Skip to main content
SpringerLink
Log in

Role of Par-4 in EMT

  • Chapter
  • First Online:
Tumor Suppressor Par-4

  • 215 Accesses

Abstract

The importance of Par-4 in apoptosis has been deciphered in depth. Interestingly, a paradigm shift is emerging with respect to the non-canonical roles of Par-4. The intricacy between Par-4 and EMT is significantly gaining traction, which is the main focus of this chapter. The chapter commences as we first delineate EMT’s transitory and dynamic nature as opposed to the conventional view that portrays EMT as unidirectional and irreversible. We have emphasized EMT’s culpability in the genesis of the metastatic program and how EMT-associated transcription factors (EMT-TFs) manipulate the cancer cells to acquire a motile phenotype suitable for intravasation, migration, and secondary metastasis. We as well discuss the molecular signaling pathways regulating EMT and the challenges rendered by the acquisition of EMT in cancer therapeutics. In the later sections, we have diligently highlighted the emergence of Par-4 as a prospective EMT nullifying candidate and therapeutic opportunities thus evolving around it. Particular emphasis is attributed to novel burgeoning role of Par-4-mediated negative regulation of the following anti-metastatic cascades; for example, modulation of β-catenin pathway, cytoskeletal rearrangements, and extracellular (ECM) remodeling and of course the anti-metastatic microRNAs. Lastly, we put forth innovative insights that link Par-4- and TGF-β-mediated lethal EMT.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Thiery JP (2002) Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454

    Article  CAS  PubMed  Google Scholar 

  2. Greenburg G, Hay ED (1988) Cytoskeleton and thyroglobulin expression change during transformation of thyroid epithelium to mesenchyme-like cells. Development 102:605–622

    Article  CAS  PubMed  Google Scholar 

  3. Thiery JP, Acloque H, Huang RY, Nieto MA (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139:871–890

    Article  CAS  PubMed  Google Scholar 

  4. Micalizzi DS, Farabaugh SM, Ford HL (2010) Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression. J Mammary Gland Biol Neoplasia 15:117–134

    Article  PubMed  PubMed Central  Google Scholar 

  5. Micalizzi DS, Ford HL (2009) Epithelial–mesenchymal transition in development and cancer. Future Oncol 5:1129–1143

    Article  PubMed  Google Scholar 

  6. Yang J, Weinberg RA (2008) Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 14:818–829

    Article  CAS  PubMed  Google Scholar 

  7. Batlle E et al (2000) The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2:84–89

    Article  CAS  PubMed  Google Scholar 

  8. Cano A et al (2000) The transcription factor snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2:76–83

    Article  CAS  PubMed  Google Scholar 

  9. Takkunen M et al (2006) Snail-dependent and-independent epithelial-mesenchymal transition in oral squamous carcinoma cells. J Histochem Cytochem 54:1263–1275

    Article  CAS  PubMed  Google Scholar 

  10. Yee DS et al (2010) The Wnt inhibitory factor 1 restoration in prostate cancer cells was associated with reduced tumor growth, decreased capacity of cell migration and invasion and a reversal of epithelial to mesenchymal transition. Mol Cancer 9:162

    Article  PubMed  PubMed Central  Google Scholar 

  11. Potts JD, Runyan RB (1989) Epithelial-mesenchymal cell transformation in the embryonic heart can be mediated, in part, by transforming growth factor β. Dev Biol 134:392–401

    Article  CAS  PubMed  Google Scholar 

  12. Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119:1420–1428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Piek E, Moustakas A, Kurisaki A, Heldin C-H, ten Dijke P (1999) TGF-(beta) type I receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cells. J Cell Sci 112:4557–4568

    Article  CAS  PubMed  Google Scholar 

  14. Moustakas A, Heldin CH (2007) Signaling networks guiding epithelial–mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci 98:1512–1520

    Article  CAS  PubMed  Google Scholar 

  15. Massagué J (2008) TGFβ in cancer. Cell 134:215–230

    Article  PubMed  PubMed Central  Google Scholar 

  16. Heldin C-H, Vanlandewijck M, Moustakas A (2012) Regulation of EMT by TGFβ in cancer. FEBS Lett 586:1959–1970

    Article  CAS  PubMed  Google Scholar 

  17. Ellenrieder V et al (2001) Transforming growth factor β1 treatment leads to an epithelial-mesenchymal transdifferentiation of pancreatic cancer cells requiring extracellular signal-regulated kinase 2 activation. Cancer Res 61:4222–4228

    CAS  PubMed  Google Scholar 

  18. Akiyoshi S et al (1999) C-ski acts as a transcriptional co-repressor in transforming growth factor-β signaling through interaction with Smads. J Biol Chem 274:35269–35277

    Article  CAS  PubMed  Google Scholar 

  19. Heldin C-H, Miyazono K, Ten Dijke P (1997) TGF-β signalling from cell membrane to nucleus through SMAD proteins. Nature 390:465–471

    Article  CAS  PubMed  Google Scholar 

  20. Nishihara A et al (1998) Role of p300, a transcriptional coactivator, in signalling of TGF-β. Genes Cells 3:613–623

    Article  CAS  PubMed  Google Scholar 

  21. Massagué J, Chen Y-G (2000) Controlling TGF-β signaling. Genes Dev 14:627–644

    Article  PubMed  Google Scholar 

  22. Feng X-H, Derynck R (2005) Specificity and versatility in TGF-β signaling through Smads. Annu Rev Cell Dev Biol 21:659–693

    Article  CAS  PubMed  Google Scholar 

  23. Garg M (2013) Epithelial-mesenchymal transition-activating transcription factors-multifunctional regulators in cancer. World J Stem cells 5:188

    Article  PubMed  PubMed Central  Google Scholar 

  24. Stemmler MP, Eccles RL, Brabletz S, Brabletz T (2019) Non-redundant functions of EMT transcription factors. Nat Cell Biol 21:102–112

    Article  CAS  PubMed  Google Scholar 

  25. Valcourt U, Kowanetz M, Niimi H, Heldin C-H, Moustakas A (2005) TGF-β and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition. Mol Biol Cell 16:1987–2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sato M, Muragaki Y, Saika S, Roberts AB, Ooshima A (2003) Targeted disruption of TGF-β1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. J Clin Invest 112:1486–1494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Saika S et al (2004) Smad3 signaling is required for epithelial-mesenchymal transition of lens epithelium after injury. Am J Pathol 164:651–663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hoot KE et al (2008) Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression. J Clin Invest 118:2722–2732

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-β family signalling. Nature 425:577–584

    Article  CAS  PubMed  Google Scholar 

  30. Davies M et al (2005) Induction of an epithelial to mesenchymal transition in human immortal and malignant keratinocytes by TGF-β1 involves MAPK, Smad and AP-1 signalling pathways. J Cell Biochem 95:918–931

    Article  CAS  PubMed  Google Scholar 

  31. Moustakas A, Heldin C-H (2005) Non-Smad TGF-β signals. J Cell Sci 118:3573–3584

    Article  CAS  PubMed  Google Scholar 

  32. Derynck R, Muthusamy BP, Saeteurn KY (2014) Signaling pathway cooperation in TGF-β-induced epithelial-mesenchymal transition. Curr Opin Cell Biol 31:56–66

    Google Scholar 

  33. Huber MA, Kraut N, Beug H (2005) Molecular requirements for epithelial–mesenchymal transition during tumor progression. Curr Opin Cell Biol 17:548–558

    Article  CAS  PubMed  Google Scholar 

  34. Xu J, Lamouille S, Derynck R (2009) TGF-β-induced epithelial to mesenchymal transition. Cell Res 19:156–172

    Article  CAS  PubMed  Google Scholar 

  35. Larue L, Bellacosa A (2005) Epithelial–mesenchymal transition in development and cancer: role of phosphatidylinositol 3′ kinase/AKT pathways. Oncogene 24:7443–7454

    Article  CAS  PubMed  Google Scholar 

  36. Conacci-Sorrell M et al (2003) Autoregulation of E-cadherin expression by cadherin–cadherin interactions: the roles of β-catenin signaling, Slug, and MAPK. J Cell Biol 163:847–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yook JI, Li X-Y, Ota I, Fearon ER, Weiss SJ (2005) Wnt-dependent regulation of the E-cadherin repressor snail. J Biol Chem 280:11740–11748

    Article  CAS  PubMed  Google Scholar 

  38. Zhou BP et al (2004) Dual regulation of snail by GSK-3β-mediated phosphorylation in control of epithelial–mesenchymal transition. Nat Cell Biol 6:931–940

    Article  CAS  PubMed  Google Scholar 

  39. Nawshad A, Medici D, Liu C-C, Hay ED (2007) TGFβ3 inhibits E-cadherin gene expression in palate medial-edge epithelial cells through a Smad2-Smad4-LEF1 transcription complex. J Cell Sci 120:1646–1653

    Article  CAS  PubMed  Google Scholar 

  40. Lucio M (2006) Notch signaling. Clin Cancer Res 12:1074–1079

    Article  Google Scholar 

  41. Wang Z, Li Y, Kong D, Sarkar FH (2010) The role of Notch signaling pathway in epithelial-mesenchymal transition (EMT) during development and tumor aggressiveness. Curr Drug Targets 11:745–751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bray SJ (2006) Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol 7:678–689

    Article  CAS  PubMed  Google Scholar 

  43. Timmerman LA et al (2004) Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev 18:99–115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Zavadil J, Cermak L, Soto-Nieves N, Böttinger EP (2004) Integration of TGF-β/Smad and Jagged1/notch signalling in epithelial-to-mesenchymal transition. EMBO J 23:1155–1165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Espinoza I, Pochampally R, Xing F, Watabe K, Miele L (2013) Notch signaling: targeting cancer stem cells and epithelial-to-mesenchymal transition. Onco Targets Ther 6:1249

    PubMed  PubMed Central  Google Scholar 

  46. Hu Y-Y, Zheng M-H, Zhang R, Liang Y-M, Han H (2012) Notch signaling in embryology and cancer. Springer, pp 186–198

    Book  Google Scholar 

  47. Wang Z et al (2010) Targeting notch signaling pathway to overcome drug resistance for cancer therapy. Biochim Biophys Acta (BBA)—reviews on Cancer 1806:258–267

    Article  CAS  Google Scholar 

  48. Sanchez A et al (2012) p38 MAPK: a mediator of hypoxia-induced cerebrovascular inflammation. J Alzheimers Dis 32:587–597

    Article  PubMed  Google Scholar 

  49. Imai T et al (2003) Hypoxia attenuates the expression of E-cadherin via up-regulation of SNAIL in ovarian carcinoma cells. Am J Pathol 163:1437–1447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Yang M-H et al (2008) Direct regulation of TWIST by HIF-1α promotes metastasis. Nat Cell Biol 10:295–305

    Article  CAS  PubMed  Google Scholar 

  51. Agani F, Jiang B-H (2013) Oxygen-independent regulation of HIF-1: novel involvement of PI3K/AKT/mTOR pathway in cancer. Curr Cancer Drug Targets 13:245–251

    Article  CAS  PubMed  Google Scholar 

  52. Minet E et al (2000) ERK activation upon hypoxia: involvement in HIF-1 activation. FEBS Lett 468:53–58

    Article  CAS  PubMed  Google Scholar 

  53. Koong AC, Chen EY, Giaccia AJ (1994) Hypoxia causes the activation of nuclear factor κB through the phosphorylation of IκBα on tyrosine residues. Cancer Res 54:1425–1430

    CAS  PubMed  Google Scholar 

  54. Tam SY, Wu VW, Law HK (2020) Hypoxia-induced epithelial-mesenchymal transition in cancers: HIF-1α and beyond. Front Oncol 10:486

    Article  PubMed  PubMed Central  Google Scholar 

  55. Lamouille S, Xu J, Derynck R (2014) Molecular mechanisms of epithelial–mesenchymal transition. Nat Rev Mol Cell Biol 15:178–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lei J et al (2013) Hedgehog signaling regulates hypoxia induced epithelial to mesenchymal transition and invasion in pancreatic cancer cells via a ligand-independent manner. Mol Cancer 12:1–11

    Article  Google Scholar 

  57. Li X-L et al (2017) Integrin β4 promotes cell invasion and epithelial-mesenchymal transition through the modulation of slug expression in hepatocellular carcinoma. Sci Rep 7:1–12

    Google Scholar 

  58. Cooper J, Giancotti FG (2019) Integrin signaling in cancer: mechanotransduction, stemness, epithelial plasticity, and therapeutic resistance. Cancer Cell 35:347–367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Soung YH, Clifford JL, Chung J (2010) Crosstalk between integrin and receptor tyrosine kinase signaling in breast carcinoma progression. BMB Rep 43:311–318

    Article  CAS  PubMed  Google Scholar 

  60. Feldkoren B, Hutchinson R, Rapoport Y, Mahajan A, Margulis V (2017) Integrin signaling potentiates transforming growth factor-beta 1 (TGF-β1) dependent down-regulation of E-cadherin expression–important implications for epithelial to mesenchymal transition (EMT) in renal cell carcinoma. Exp Cell Res 355:57–66

    Article  CAS  PubMed  Google Scholar 

  61. Desgrosellier JS, Cheresh DA (2010) Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 10:9–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Trusolino L, Bertotti A, Comoglio PM (2001) A signaling adapter function for α6β4 integrin in the control of HGF-dependent invasive growth. Cell 107:643–654

    Article  CAS  PubMed  Google Scholar 

  63. Abba ML, Patil N, Leupold JH, Allgayer H (2016) MicroRNA regulation of epithelial to mesenchymal transition. J Clin Med 5:8

    Article  PubMed Central  Google Scholar 

  64. Wagner S, Ngezahayo A, Murua Escobar H, Nolte I (2014) Role of miRNA let-7 and its major targets in prostate cancer. Biomed Res Int 2014:376326

    Article  PubMed  PubMed Central  Google Scholar 

  65. Sheedy P, Medarova Z (2018) The fundamental role of miR-10b in metastatic cancer. Am J Cancer Res 8:1674

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Zhang J, Ma L (2012) MicroRNA control of epithelial–mesenchymal transition and metastasis. Cancer Metastasis Rev 31:653–662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Xu D et al (2011) miR-22 represses cancer progression by inducing cellular senescence. J Cell Biol 193:409–424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Xiao B, Shi X, Bai J (2019) miR-30a regulates the proliferation and invasion of breast cancer cells by targeting snail. Oncol Lett 17:406–413

    CAS  PubMed  Google Scholar 

  69. Nie D, Fu J, Chen H, Cheng J, Fu J (2019) Roles of microRNA-34a in epithelial to mesenchymal transition, competing endogenous RNA sponging and its therapeutic potential. Int J Mol Sci 20:861

    Article  CAS  PubMed Central  Google Scholar 

  70. Brabletz S, Brabletz T (2010) The ZEB/miR-200 feedback loop—a motor of cellular plasticity in development and cancer? EMBO Rep 11:670–677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Nairismägi M-L, Füchtbauer A, Labouriau R, Bramsen JB, Füchtbauer E-M (2013) The proto-oncogene TWIST1 is regulated by microRNAs. PLoS One 8:e66070

    Article  PubMed  PubMed Central  Google Scholar 

  72. Wei F, Cao C, Xu X, Wang J (2015) Diverse functions of miR-373 in cancer. J Transl Med 13:1–8

    Article  CAS  Google Scholar 

  73. Si M et al (2007) miR-21-mediated tumor growth. Oncogene 26:2799–2803

    Article  CAS  PubMed  Google Scholar 

  74. Han M et al (2012) Antagonism of miR-21 reverses epithelial-mesenchymal transition and cancer stem cell phenotype through AKT/ERK1/2 inactivation by targeting PTEN. PLoS One 7:e39520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Wang H et al (2019) microRNA-21 promotes breast cancer proliferation and metastasis by targeting LZTFL1. BMC cancer 19:738

    Article  PubMed  PubMed Central  Google Scholar 

  76. Wang Y, Li Z, Zhao X, Zuo X, Peng Z (2016) miR-10b promotes invasion by targeting HOXD10 in colorectal cancer. Oncol Lett 12:488–494

    Article  PubMed  PubMed Central  Google Scholar 

  77. Ma L et al (2010) miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol 12:247–256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Gwak JM et al (2014) MicroRNA-9 is associated with epithelial-mesenchymal transition, breast cancer stem cell phenotype, and tumor progression in breast cancer. Breast Cancer Res Treat 147:39–49

    Article  CAS  PubMed  Google Scholar 

  79. Martello G et al (2010) A MicroRNA targeting dicer for metastasis control. Cell 141:1195–1207

    Article  CAS  PubMed  Google Scholar 

  80. Burk U et al (2008) A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep 9:582–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Jang K et al (2014) Loss of microRNA-200a expression correlates with tumor progression in breast cancer. Transl Res 163:242–251

    Article  CAS  PubMed  Google Scholar 

  82. Korpal M, Ell BJ, Buffa FM, Ibrahim T, Blanco MA, Celià-Terrassa T et al (2011) Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med 17:1101–1108

    Google Scholar 

  83. Bae E et al (2014) Definition of smad3 phosphorylation events that affect malignant and metastatic behaviors in breast cancer cells. Cancer Res 74:6139–6149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Hong S et al (2014) SHOX2 is a direct miR-375 target and a novel epithelial-to-mesenchymal transition inducer in breast cancer cells. Neoplasia 16:279–290. e275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Arora H, Qureshi R, Park WY (2013) miR-506 Regulates Epithelial Mesenchymal Transition in Breast Cancer Cell Lines. PLoS One 8(5):e64273

    Google Scholar 

  86. Moes M et al (2012) A novel network integrating a miRNA-203/SNAI1 feedback loop which regulates epithelial to mesenchymal transition. PLoS One 7:e35440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Ding X, Park SI, McCauley LK, Wang CY (2013) Signaling between transforming growth factor β (TGF-β) and transcription factor SNAI2 represses expression of microRNA miR-203 to promote epithelialmesenchymal transition and tumor metastasis. J Biol Chem 288:10241–10253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Siemens H, Jackstadt R, Hünten S, Kaller M, Menssen A, Gotz U, Hermeking H (2011) miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions. Cell Cycle 10:4256–4271

    Article  CAS  PubMed  Google Scholar 

  89. Jeanes A, Gottardi C, Yap A (2008) Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene 27:6920–6929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Kwon MJ (2013) Emerging roles of claudins in human cancer. Int J Mol Sci 14:18148–18180

    Article  PubMed  PubMed Central  Google Scholar 

  91. Salvador E, Burek M, Förster CY (2016) Tight junctions and the tumor microenvironment. Curr Pathobiol Rep 4:135–145

    Article  PubMed  PubMed Central  Google Scholar 

  92. Loh C-Y et al (2019) The E-cadherin and N-cadherin switch in epithelial-to-mesenchymal transition: signaling, therapeutic implications, and challenges. Cell 8:1118

    Article  CAS  Google Scholar 

  93. Mendez MG, Kojima SI, Goldman RD (2010) Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. FASEB J 24:1838–1851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Scott LE, Weinberg SH, Lemmon CA (2019) Mechanochemical signaling of the extracellular matrix in epithelial-mesenchymal transition. Front Cell Dev Biol 7:135

    Article  PubMed  PubMed Central  Google Scholar 

  95. Wang Y, Shi J, Chai K, Ying X, Zhou PB (2013) The role of snail in EMT and tumorigenesis. Curr Cancer Drug Targets 13:963–972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Kang Y, Massagué J (2004) Epithelial-mesenchymal transitions: twist in development and metastasis. Cell 118:277–279

    Article  CAS  PubMed  Google Scholar 

  97. Vandewalle C, Van Roy F, Berx G (2009) The role of the ZEB family of transcription factors in development and disease. Cell Mol Life Sci 66:773–787

    Article  CAS  PubMed  Google Scholar 

  98. Wu Q, Wang J, Liu Y, Gong X (2019) Epithelial cell adhesion molecule and epithelial-mesenchymal transition are associated with vasculogenic mimicry, poor prognosis, and metastasis of triple negative breast cancer. Int J Clin Exp Pathol 12:1678

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Knights AJ, Funnell AP, Crossley M, Pearson RC (2012) Holding tight: cell junctions and cancer spread. Trends Cancer Res 8:61

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Berx G, Van Roy F (2009) Involvement of members of the cadherin superfamily in cancer. Cold Spring Harb Perspect Biol 1:a003129

    Article  PubMed  PubMed Central  Google Scholar 

  101. Winter JM et al (2008) Absence of E-cadherin expression distinguishes noncohesive from cohesive pancreatic cancer. Clin Cancer Res 14:412–418

    Article  CAS  PubMed  Google Scholar 

  102. Liu J et al (2016) CDH1 promoter methylation correlates with decreased gene expression and poor prognosis in patients with breast cancer. Oncol Lett 11:2635–2643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Lin X, Shang X, Manorek G, Howell SB (2013) Regulation of the epithelial-mesenchymal transition by claudin-3 and claudin-4. PLoS One 8:e67496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Singh AB, Sharma A, Dhawan P (2010) Claudin family of proteins and cancer: an overview. J Oncol 2010:541957

    Article  PubMed  PubMed Central  Google Scholar 

  105. Porta-De-La-Riva M et al (2011) TFCP2c/LSF/LBP-1c is required for Snail1-induced fibronectin gene expression. Biochem J 435:563–568

    Article  CAS  PubMed  Google Scholar 

  106. Mrozik KM, Blaschuk OW, Cheong CM, Zannettino ACW, Vandyke K (2018) N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer. BMC Cancer 18:939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Sadot E, Simcha I, Shtutman M, Ben-Ze’ev A, Geiger B (1998) Inhibition of β-catenin-mediated transactivation by cadherin derivatives. Proc Natl Acad Sci 95:15339–15344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Zhang B et al (2013) Microenvironmental protection of CML stem and progenitor cells from tyrosine kinase inhibitors through N-cadherin and Wnt–β-catenin signaling. Blood 121:1824–1838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Qian X et al (2014) N-cadherin/FGFR promotes metastasis through epithelial-to-mesenchymal transition and stem/progenitor cell-like properties. Oncogene 33:3411–3421

    Article  CAS  PubMed  Google Scholar 

  110. Polioudaki H, Agelaki S, Chiotaki R, Politaki E, Mavroudis D, Matikas A, Georgoulias V, Theodoropoulos PA (2015) Variable expression levels of keratin and vimentin reveal differential EMT status of circulating tumor cells and correlation with clinical characteristics and outcome of patients with metastatic breast cancer. BMC Cancer 15:399. https://doi.org/10.1186/s12885-015-1386-7

  111. Satelli A, Li S (2011) Vimentin in cancer and its potential as a molecular target for cancer therapy. Cell Mol Life Sci 68:3033–3046

    Google Scholar 

  112. Heerboth S et al (2015) EMT and tumor metastasis. Clin Transl Med 4:6

    Article  PubMed  PubMed Central  Google Scholar 

  113. Ward K et al (2015) Epithelial cell adhesion molecule is expressed in a subset of sarcomas and correlates to the degree of cytological atypia in leiomyosarcomas. Mol Clin Oncol 3:31–36

    Article  PubMed  Google Scholar 

  114. Soysal SD et al (2013) EpCAM expression varies significantly and is differentially associated with prognosis in the luminal B HER2+, basal-like, and HER2 intrinsic subtypes of breast cancer. Br J Cancer 108:1480–1487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Abd El-Maqsoud NM, Abd El-Rehim DM (2014) Clinicopathologic implications of EpCAM and Sox2 expression in breast cancer. Clin Breast Cancer 14:e1–e9

    Article  CAS  PubMed  Google Scholar 

  116. González B, Denzel S, Mack B, Conrad M, Gires O (2009) EpCAM is involved in maintenance of the murine embryonic stem cell phenotype. Stem Cells 27:1782–1791

    Article  PubMed  Google Scholar 

  117. Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12:895–904

    Article  CAS  PubMed  Google Scholar 

  118. Valastyan S, Weinberg RA (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147:275–292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Sedgwick AE, D’Souza-Schorey C (2016) Wnt signaling in cell motility and invasion: drawing parallels between development and cancer. Cancers 8:80

    Article  PubMed Central  Google Scholar 

  120. Sahlgren C, Gustafsson MV, Jin S, Poellinger L, Lendahl U (2008) Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci 105:6392–6397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Eckert MA et al (2011) Twist1-induced invadopodia formation promotes tumor metastasis. Cancer Cell 19:372–386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Murphy DA et al (2011) A Src-Tks5 pathway is required for neural crest cell migration during embryonic development. PLoS One 6:e22499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Pignatelli J, Tumbarello DA, Schmidt RP, Turner CE (2012) Hic-5 promotes invadopodia formation and invasion during TGF-β–induced epithelial–mesenchymal transition. J Cell Biol 197:421–437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Slorach EM, Chou J, Werb Z (2011) Zeppo1 is a novel metastasis promoter that represses E-cadherin expression and regulates p120-catenin isoform expression and localization. Genes Dev 25:471–484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Peinado H, Olmeda D, Cano A (2007) Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 7:415–428

    Article  CAS  PubMed  Google Scholar 

  126. Shenoy AK, Lu J (2016) Cancer cells remodel themselves and vasculature to overcome the endothelial barrier. Cancer Lett 380:534–544

    Article  CAS  PubMed  Google Scholar 

  127. Qi J, Wang J, Romanyuk O, Siu C-H (2006) Involvement of Src family kinases in N-cadherin phosphorylation and β-catenin dissociation during transendothelial migration of melanoma cells. Mol Biol Cell 17:1261–1272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Hamidi H, Ivaska J (2018) Every step of the way: integrins in cancer progression and metastasis. Nat Rev Drug Discov 17:31–46

    Google Scholar 

  129. Barthel SR, Gavino JD, Descheny L, Dimitroff CJ (2007) Targeting selectins and selectin ligands in inflammation and cancer. Expert Opin Ther Targets 11:1473–1491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Drake JM, Strohbehn G, Bair TB, Moreland JG, Henry MD (2009) ZEB1 enhances transendothelial migration and represses the epithelial phenotype of prostate cancer cells. Mol Biol Cell 20:2207–2217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Gilles C, Newgreen DF, Sato H, Thompson EW (2005) Rise and fall of epithelial phenotype. Springer, pp 297–315

    Book  Google Scholar 

  132. Tsuji T et al (2008) Epithelial-mesenchymal transition induced by growth suppressor p12CDK2-AP1 promotes tumor cell local invasion but suppresses distant colony growth. Cancer Res 68:10377–10386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Tsuji T, Ibaragi S, Hu G-F (2009) Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res 69:7135–7139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Kim Y-N, Koo KH, Sung JY, Yun U-J, Kim H (2012) Anoikis resistance: an essential prerequisite for tumor metastasis. Int J Cell Biol 2012:306879

    Article  PubMed  PubMed Central  Google Scholar 

  135. Vachon PH (2011) Integrin signaling, cell survival, and anoikis: distinctions, differences, and differentiation. J Signal Transduction 2011

    Google Scholar 

  136. Tsai JH, Yang J (2013) Epithelial–mesenchymal plasticity in carcinoma metastasis. Genes Dev 27:2192–2206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Rhim AD et al (2012) EMT and dissemination precede pancreatic tumor formation. Cell 148:349–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Stegner D, Dütting S, Nieswandt B (2014) Mechanistic explanation for platelet contribution to cancer metastasis. Thromb Res 133:S149–S157

    Article  CAS  PubMed  Google Scholar 

  139. Lou X-L et al (2015) Interaction between circulating cancer cells and platelets: clinical implication. Chin J Cancer Res 27:450

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Kopp H-G, Placke T, Salih HR (2009) Platelet-derived transforming growth factor-β down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res 69:7775–7783

    Article  CAS  PubMed  Google Scholar 

  141. Vivier E, Ugolini S, Blaise D, Chabannon C, Brossay L (2012) Targeting natural killer cells and natural killer T cells in cancer. Nat Rev Immunol 12:239–252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Placke T et al (2012) Platelet-derived MHC class I confers a pseudonormal phenotype to cancer cells that subverts the antitumor reactivity of natural killer immune cells. Cancer Res 72:440–448

    Article  CAS  PubMed  Google Scholar 

  143. Palucka K, Banchereau J (2012) Cancer immunotherapy via dendritic cells. Nat Rev Cancer 12:265–277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Whipple RA et al (2010) Epithelial-to-mesenchymal transition promotes tubulin detyrosination and microtentacles that enhance endothelial engagement. Cancer Res 70:8127–8137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Matrone MA et al (2010) Metastatic breast tumors express increased tau, which promotes microtentacle formation and the reattachment of detached breast tumor cells. Oncogene 29:3217–3227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Fishbein L et al (2017) Comprehensive molecular characterization of pheochromocytoma and paraganglioma. Cancer Cell 31:181–193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Cao Y, Hoeppner LH, Bach S, E G, Guo Y, Wang E et al (2013) Neuropilin-2 promotes extravasation and metastasis by interacting with endothelial α5 Integrin. Cancer Res 73(14):4579-4590

    Google Scholar 

  148. Stoletov K et al (2010) Visualizing extravasation dynamics of metastatic tumor cells. J Cell Sci 123:2332–2341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Bonnomet A et al (2012) A dynamic in vivo model of epithelial-to-mesenchymal transitions in circulating tumor cells and metastases of breast cancer. Oncogene 31:3741–3753

    Article  CAS  PubMed  Google Scholar 

  150. Ocaña OH et al (2012) Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell 22:709–724

    Article  PubMed  Google Scholar 

  151. Mejlvang J et al (2007) Direct repression of cyclin D1 by SIP1 attenuates cell cycle progression in cells undergoing an epithelial mesenchymal transition. Mol Biol Cell 18:4615–4624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Korpal M et al (2011) Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med 17:1101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Gupta PB, Chaffer CL, Weinberg RA (2009) Cancer stem cells: mirage or reality? Nat Med 15:1010–1012

    Article  CAS  PubMed  Google Scholar 

  154. Aponte PM, Caicedo A (2017) Stemness in cancer: stem cells, cancer stem cells, and their microenvironment. Stem Cells Int 2017:5619472

    Article  PubMed  PubMed Central  Google Scholar 

  155. Bao B, Ahmad A, Azmi AS, Ali S, Sarkar FH (2013) Overview of cancer stem cells (CSCs) and mechanisms of their regulation: implications for cancer therapy. Curr Protoc Pharmacol 61:14.25.11–14.25.14

    Article  Google Scholar 

  156. Rosen JM, Jordan CT (2009) The increasing complexity of the cancer stem cell paradigm. Science 324:1670–1673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Najafi M, Farhood B, Mortezaee K (2019) Cancer stem cells (CSCs) in cancer progression and therapy. J Cell Physiol 234:8381–8395

    Article  CAS  PubMed  Google Scholar 

  158. Jaggupilli A, Elkord E (2012) Significance of CD44 and CD24 as cancer stem cell markers: an enduring ambiguity. Clin Dev Immunol 2012

    Google Scholar 

  159. Chang C-J et al (2011) p53 regulates epithelial–mesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol 13:317–323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Burikhanov R et al (2009) The tumor suppressor Par-4 activates an extrinsic pathway for apoptosis. Cell 138:377–388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Wang G et al (2012) Astrocytes secrete exosomes enriched with proapoptotic ceramide and prostate apoptosis response 4 (PAR-4) potential mechanism of apoptosis induction in Alzheimer disease (AD). J Biol Chem 287:21384–21395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Srinivasan S, Ranga RS, Burikhanov R, Han S-S, Chendil D (2007) Par-4-dependent apoptosis by the dietary compound withaferin A in prostate cancer cells. Cancer Res 67:246–253

    Article  CAS  PubMed  Google Scholar 

  163. Gurumurthy S, Goswami A, Vasudevan KM, Rangnekar VM (2005) Phosphorylation of Par-4 by protein kinase A is critical for apoptosis. Mol Cell Biol 25:1146–1161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Rasool RU et al (2016) A journey beyond apoptosis: new enigma of controlling metastasis by pro-apoptotic Par-4. Clin Exp Metastasis 33:757–764

    Article  PubMed  Google Scholar 

  165. Zhao Y et al (2007) Cancer resistance in transgenic mice expressing the SAC module of Par-4. Cancer Res 67:9276–9285

    Article  CAS  PubMed  Google Scholar 

  166. El-Guendy N, Zhao Y, Gurumurthy S, Burikhanov R, Rangnekar VM (2003) Identification of a unique core domain of par-4 sufficient for selective apoptosis induction in cancer cells. Mol Cell Biol 23:5516–5525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Park MH, Hong JT (2016) Roles of NF-κB in cancer and inflammatory diseases and their therapeutic approaches. Cell 5:15

    Article  Google Scholar 

  168. Saegusa M, Hashimura M, Kuwata T, Okayasu I (2010) Transcriptional regulation of pro-apoptotic Par-4 by NF-κB/p65 and its function in controlling cell kinetics during early events in endometrial tumourigenesis. J Pathol 221:26–36

    Article  CAS  PubMed  Google Scholar 

  169. Zhao Y, Rangnekar VM (2008) Apoptosis and tumor resistance conferred by Par-4. Cancer Biol Ther 7:1867–1874

    Article  CAS  PubMed  Google Scholar 

  170. Zhang X, Tang N, Hadden TJ, Rishi AK (2011) Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta (BBA)-Mol Cell Res 1813:1978–1986

    Article  CAS  Google Scholar 

  171. Joshi J et al (2008) Par-4 inhibits Akt and suppresses Ras-induced lung tumorigenesis. EMBO J 27:2181–2193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Cantley LC (2002) The phosphoinositide 3-kinase pathway. Science 296:1655–1657

    Article  CAS  PubMed  Google Scholar 

  173. Chaudhry P et al (2014) Prostate apoptosis response-4 mediates TGF-β-induced epithelial-to-mesenchymal transition. Cell Death Dis 5:e1044–e1044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Lin A, Karin M Seminars in cancer biology. Elsevier, pp 107–114

    Google Scholar 

  175. Hebbar N, Wang C, Rangnekar VM (2012) Mechanisms of apoptosis by the tumor suppressor Par-4. J Cell Physiol 227:3715–3721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Nalla AK, Gorantla B, Gondi CS, Lakka SS, Rao JS (2010) Targeting MMP-9, uPAR, and cathepsin B inhibits invasion, migration and activates apoptosis in prostate cancer cells. Cancer Gene Ther 17:599–613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Rah B et al (2012) A novel MMP-2 inhibitor 3-azidowithaferin A (3-azidoWA) abrogates cancer cell invasion and angiogenesis by modulating extracellular Par-4. PLoS One 7:e44039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Chaudhry P, Singh M, Parent S, Asselin E (2012) Prostate apoptosis response 4 (Par-4), a novel substrate of caspase-3 during apoptosis activation. Mol Cell Biol 32:826–839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Ur Rasool R et al (2016) Dual modulation of Ras-Mnk and PI3K-AKT-mTOR pathways: a novel c-FLIP inhibitory mechanism of 3-AWA mediated translational attenuation through dephosphorylation of eIF4E. Sci Rep 6:18800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Pires BR et al (2017) NF-kappaB is involved in the regulation of EMT genes in breast cancer cells. PLoS One 12:e0169622

    Article  PubMed  PubMed Central  Google Scholar 

  181. Amin H et al (2016) Par-4 dependent modulation of cellular β-catenin by medicinal plant natural product derivative 3-azido Withaferin A. Mol Carcinog 55:864–881

    Article  CAS  PubMed  Google Scholar 

  182. Qin Q, Xu Y, He T, Qin C, Xu J (2012) Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms. Cell Res 22:90–106

    Article  CAS  PubMed  Google Scholar 

  183. Yang J, Mani SA, Weinberg RA (2006) Exploring a new twist on tumor metastasis. Cancer Res 66:4549–4552

    Article  CAS  PubMed  Google Scholar 

  184. Zhao Z, Rahman MA, Chen ZG, Shin DM (2017) Multiple biological functions of Twist1 in various cancers. Oncotarget 8:20380

    Article  PubMed  PubMed Central  Google Scholar 

  185. Katoch A et al (2020) Overlapping targets exist between the Par-4 and miR-200c axis which regulate EMT and proliferation of pancreatic cancer cells. Transl Oncol 14:100879

    Article  PubMed  PubMed Central  Google Scholar 

  186. Katoch A et al (2018) Dual role of Par-4 in abrogation of EMT and switching on mesenchymal to epithelial transition (MET) in metastatic pancreatic cancer cells. Mol Carcinog 57:1102–1115

    Article  CAS  PubMed  Google Scholar 

  187. Vichalkovski A, Gresko E, Hess D, Restuccia D, Hemmings B (2010) PKB/AKT phosphorylation of the transcription factor Twist-1 at Ser42 inhibits p53 activity in response to DNA damage. Oncogene 29:3554–3565

    Article  CAS  PubMed  Google Scholar 

  188. Pham CG et al (2007) Upregulation of Twist-1 by NF-κB blocks cytotoxicity induced by chemotherapeutic drugs. Mol Cell Biol 27:3920–3935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Li C-W et al (2012) Epithelial–mesenchymal transition induced by TNF-α requires NF-κB–mediated transcriptional upregulation of Twist1. Cancer Res 72:1290–1300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Burikhanov R et al (2014) Arylquins target vimentin to trigger Par-4 secretion for tumor cell apoptosis. Nat Chem Biol 10:924–926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Moon RT, Bowerman B, Boutros M, Perrimon N (2002) The promise and perils of Wnt signaling through β-catenin. Science 296:1644–1646

    Article  CAS  PubMed  Google Scholar 

  192. Beurel E, Grieco SF, Jope RS (2015) Glycogen synthase kinase-3 (GSK3): regulation, actions, and diseases. Pharmacol Ther 148:114–131

    Article  CAS  PubMed  Google Scholar 

  193. David CJ et al (2016) TGF-β tumor suppression through a lethal EMT. Cell 164:1015–1030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Mohd Faheem M et al (2020) Par-4 mediated Smad4 induction in PDAC cells restores canonical TGF-β/Smad4 axis driving the cells towards lethal EMT. Eur J Cell Biol 99:151076

    Article  CAS  PubMed  Google Scholar 

  195. Marino N, Marshall J-C, Steeg PS (2011) Protein–protein interactions: a mechanism regulating the anti-metastatic properties of Nm23-H1. Naunyn Schmiedeberg's Arch Pharmacol 384:351–362

    Article  CAS  Google Scholar 

  196. Jung H, Seong H-A, Ha H (2007) NM23-H1 tumor suppressor and its interacting partner STRAP activate p53 function. J Biol Chem 282:35293–35307

    Article  CAS  PubMed  Google Scholar 

  197. Seong H-A, Jung H, Ha H (2007) NM23-H1 tumor suppressor physically interacts with serine-threonine kinase receptor-associated protein, a transforming growth factor-β (TGF-β) receptor-interacting protein, and negatively regulates TGF-β signaling. J Biol Chem 282:12075–12096

    Article  CAS  PubMed  Google Scholar 

  198. Rahman MS, Akhtar N, Jamil HM, Banik RS, Asaduzzaman SM (2015) TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation. Bone Res 3:15005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Buijs JT et al (2007) TGF-β and BMP7 interactions in tumour progression and bone metastasis. Clin Exp Metastasis 24:609–617

    Article  CAS  PubMed  Google Scholar 

  200. Macı́as-Silva M, Hoodless PA, Tang SJ, Buchwald M, Wrana JL (1998) Specific activation of Smad1 signaling pathways by the BMP7 type I receptor, ALK2. J Biol Chem 273:25628–25636

    Article  PubMed  Google Scholar 

  201. Fukuda T et al (2009) Constitutively activated ALK2 and increased SMAD1/5 cooperatively induce bone morphogenetic protein signaling in fibrodysplasia ossificans progressiva. J Biol Chem 284:7149–7156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Vannini I, Fanini F, Fabbri M (2018) Emerging roles of microRNAs in cancer. Curr Opin Genet Dev 48:128–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Lou W et al (2017) MicroRNAs in cancer metastasis and angiogenesis. Oncotarget 8:115787

    Article  PubMed  PubMed Central  Google Scholar 

  204. Lu D, Tang L, Zhuang Y, Zhao P (2018) miR-17-3P regulates the proliferation and survival of colon cancer cells by targeting Par4. Mol Med Rep 17:618–623

    CAS  PubMed  Google Scholar 

  205. Paterson EL et al (2013) Down-regulation of the miRNA-200 family at the invasive front of colorectal cancers with degraded basement membrane indicates EMT is involved in cancer progression. Neoplasia 15:180–IN122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Korpal M, Kang Y (2008) The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol 5:115–119

    Article  CAS  PubMed  Google Scholar 

  207. Hur K et al (2013) MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis. Gut 62:1315–1326

    Article  CAS  PubMed  Google Scholar 

  208. Bai WD et al (2014) MiR-200c suppresses TGF-β signaling and counteracts trastuzumab resistance and metastasis by targeting ZNF217 and ZEB1 in breast cancer. Int J Cancer 135:1356–1368

    Article  CAS  PubMed  Google Scholar 

  209. Mutlu M et al (2016) miR-200c: a versatile watchdog in cancer progression, EMT, and drug resistance. J Mol Med 94:629–644

    Article  CAS  PubMed  Google Scholar 

  210. Hüsemann Y et al (2008) Systemic spread is an early step in breast cancer. Cancer Cell 13:58–68

    Article  PubMed  Google Scholar 

  211. Ansieau S et al (2008) Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell 14:79–89

    Article  CAS  PubMed  Google Scholar 

  212. Valsesia-Wittmann S et al (2004) Oncogenic cooperation between H-Twist and N-Myc overrides failsafe programs in cancer cells. Cancer Cell 6:625–630

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Mir Mohd Faheem and Archana Katoch contributed equally to this work.

Authors and Affiliations

  1. Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, Jammu and Kashmir, India

    Mir Mohd Faheem, Archana Katoch & Anindya Goswami

  2. School of Biotechnology, University of Jammu, Jammu, Jammu and Kashmir, India

    Mir Mohd Faheem

  3. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India

    Archana Katoch & Anindya Goswami

Authors
  1. Mir Mohd Faheem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Archana Katoch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anindya Goswami
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anindya Goswami .

Editor information

Editors and Affiliations

  1. Assoc Dir, Markey Cancer Center, Univ of Kentucky, Lexington, KY, USA

    Vivek M. Rangnekar

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Faheem, M.M., Katoch, A., Goswami, A. (2021). Role of Par-4 in EMT. In: Rangnekar, V.M. (eds) Tumor Suppressor Par-4. Springer, Cham. https://doi.org/10.1007/978-3-030-80558-6_1

Download citation

Publish with us

Policies and ethics

Search

Navigation