Advertisement

Tumor Biology

, Volume 35, Issue 8, pp 7335–7342 | Cite as

Epithelial to mesenchymal transition inducing transcription factors and metastatic cancer

  • Mousumi Tania
  • Md. Asaduzzaman Khan
  • Junjiang Fu
Review

Abstract

The epithelial to mesenchymal transition (EMT) is an important step for the developmental process. Recent evidences support that EMT allows the tumor cells to acquire invasive properties and to develop metastatic growth characteristics. Some of the transcription factors, which are actively involved in EMT process, have a significant role in the EMT–metastasis linkage. A number of studies have reported that EMT-inducing transcription factors (EMT-TFs), such as Twist, Snail, Slug, and Zeb, are directly or indirectly involved in cancer cell metastasis through a different signaling cascades, including the Akt, signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase (MAPK) and Wnt pathways, with the ultimate consequence of the downregulation of E-cadherin and upregulation of metastatic proteins, such as N-cadherin, vimentin, matrix metalloproteinase (MMP)-2, etc. This review summarizes the update information on the association of EMT-TFs with cancer metastasis and the possible cancer therapeutics via targeting the EMT-TFs.

Keywords

Epithelial to mesenchymal transition Metastasis Twist Snail Slug Zeb Cancer therapeutics 

Notes

Acknowledgments

This work was supported in part by the National Natural Science Foundation of China (81172049), Science and Technology Innovation Team of Colleges and Universities of Sichuan Province (13TD0032), Health Department Foundation of Sichuan Province (130261), The Research Foundation of the Science and Technology Department of Sichuan Province (14JC0797), Luzhou City special foundation (2013LZLY-J10), and Luzhou Medical College grants for postdoctoral research (20130512, 20130513).

Conflicts of interest

None

References

  1. 1.
    Wang Y, Zhou BP. Epithelial-mesenchymal transition in breast cancer progression and metastasis. Chin J Cancer. 2011;30:603–11.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Yang G, Yuan J, Li K. EMT transcription factors: implication in osteosarcoma. Med Oncol. 2013;30:697.PubMedCrossRefGoogle Scholar
  3. 3.
    Kang Y, Massagué J. Epithelial-mesenchymal transitions: twist in development and metastasis. Cell. 2004;118:277–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Khan MA, Chen HC, Zhang D, Fu J. Twist: a molecular target in cancer therapeutics. Tumor Biol. 2013;34:2497–506.CrossRefGoogle Scholar
  5. 5.
    Khan MI, Adhami VM, Lall RK, Sechi M, Joshi DC, Haider OM, et al. YB-1 expression promotes epithelial-to-mesenchymal transition in prostate cancer that is inhibited by a small molecule fisetin. Oncotarget. 2014 Feb 19. (in press).Google Scholar
  6. 6.
    Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science. 2011;331:1559–64.PubMedCrossRefGoogle Scholar
  7. 7.
    Martin TA, Goyal A, Watkins G, Jiang WG. Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Ann Surg Oncol. 2005;12:488–96.PubMedCrossRefGoogle Scholar
  8. 8.
    De Craene B, Berx G. Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 2013;13:97–110.PubMedCrossRefGoogle Scholar
  9. 9.
    Garg M. Epithelial-mesenchymal transition—activating transcription factors—multifunctional regulators in cancer. World J Stem Cells. 2013;5:188–95.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Yin K, Liao Q, He H, Zhong D. Prognostic value of Twist and E-cadherin in patients with osteosarcoma. Med Oncol. 2012;29:3449–55.PubMedCrossRefGoogle Scholar
  11. 11.
    Šošić D, Richardson JA, Yu K, Ornitz DM, Olson EN. Twist regulates cytokine gene expression through a negative feedback loop that represses NF-kappaB activity. Cell. 2003;112:169–80.PubMedCrossRefGoogle Scholar
  12. 12.
    Horvai AE, Roy R, Borys D, O’Donnell RJ. Regulators of skeletal development: a cluster analysis of 206 bone tumors reveals diagnostically useful markers. Mod Pathol. 2012;25:1452–61.PubMedCrossRefGoogle Scholar
  13. 13.
    Lee MS, Lowe G, Flanagan S, Kuchler K, Glackin CA. Human Dermo-1 has attributes similar to twist in early bone development. Bone. 2000;27:591–602.PubMedCrossRefGoogle Scholar
  14. 14.
    Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004;117:927–39.PubMedCrossRefGoogle Scholar
  15. 15.
    Sahlin P, Windh P, Lauritzen C, Emanuelsson M, Grönberg H, Stenman G. Women with Saethre-Chotzen syndrome are at increased risk of breast cancer. Gene Chromosome Cancer. 2007;46:656–60.CrossRefGoogle Scholar
  16. 16.
    Gort EH, Suijkerbuijk KP, Roothaan SM, Raman V, Vooijs M, van der Wall E, et al. Methylation of the TWIST1 promoter, TWIST1 mRNA levels, and immunohistochemical expression of TWIST1 in breast cancer. Cancer Epidemiol Biomark Prev. 2008;17:3325–30.CrossRefGoogle Scholar
  17. 17.
    Mehrotra J, Vali M, McVeigh M, Kominsky SL, Fackler MJ, Lahti-Domenici J, et al. Very high frequency of hypermethylated genes in breast cancer metastasis to the bone, brain, and lung. Clin Cancer Res. 2004;10:3104–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Okada T, Suehiro Y, Ueno K, Mitomori S, Kaneko S, Nishioka M, et al. TWIST1 hypermethylation is observed frequently in colorectal tumors and its overexpression is associated with unfavorable outcomes in patients with colorectal cancer. Gene Chromosome Cancer. 2010;49:452–62.Google Scholar
  19. 19.
    Locke I, Kote-Jarai Z, Fackler MJ, Bancroft E, Osin P, Nerurkar A, et al. Gene promoter hypermethylation in ductal lavage fluid from healthy BRCA gene mutation carriers and mutation-negative controls. Breast Cancer Res. 2007;9(1):R20.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Fu J, Zhang L, He T, Xiao X, Liu X, Wang L, et al. TWIST represses estrogen receptor-alpha expression by recruiting the NuRD protein complex in breast cancer cells. Int J Biol Sci. 2012;8:522–32.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Zhao XL, Sun T, Che N, Sun D, Zhao N, Dong XY. Promotion of hepatocellular carcinoma metastasis through matrix metalloproteinase activation by epithelial-mesenchymal transition regulator Twist1. J Cell Mol Med. 2011;15:691–700.PubMedCrossRefGoogle Scholar
  22. 22.
    Okamura H, Yoshida K, Haneji T. Negative regulation of TIMP1 is mediated by transcription factor TWIST1. Int J Oncol. 2009;35:181–6.PubMedGoogle Scholar
  23. 23.
    Fu J, Qin L, He T, Qin J, Hong J, Wong J, et al. The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis. Cell Res. 2011;21:275–89.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Yang MH, Hsu DS, Wang HW, Wang HJ, Lan HY, Yang WH, et al. Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition. Nat Cell Biol. 2010;12:982–92.PubMedCrossRefGoogle Scholar
  25. 25.
    Li J, Zhou BP. Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters. BMC Cancer. 2011;11:49.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Wang Y, Shi J, Chai K, Ying X, Zhou BP. The role of Snail in EMT and tumorigenesis. Curr Cancer Drug Targets. 2013;13:963–72.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Barrallo-Gimeno A, Nieto MA. The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development. 2005;132:3151–61.PubMedCrossRefGoogle Scholar
  28. 28.
    Peinado H, Ballestar E, Esteller M, Cano A. Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex. Mol Cell Biol. 2004;24:306–19.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Kurrey NK, Jalgaonkar SP, Joglekar AV, Ghanate AD, Chaskar PD, Doiphode RY, et al. Snail and slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem Cells. 2009;27(9):2059–68.PubMedCrossRefGoogle Scholar
  30. 30.
    Gheldof A, Hulpiau P, van Roy F, De Craene B, Berx G. Evolutionary functional analysis and molecular regulation of the ZEB transcription factors. Cell Mol Life Sci. 2012;69:2527–41.PubMedCrossRefGoogle Scholar
  31. 31.
    Browne G, Sayan AE, Tulchinsky E. ZEB proteins link cell motility with cell cycle control and cell survival in cancer. Cell Cycle. 2010;9:886–91.PubMedCrossRefGoogle Scholar
  32. 32.
    Sánchez-Tilló E, Siles L, de Barrios O, Cuatrecasas M, Vaquero EC, Castells A, et al. Expanding roles of ZEB factors in tumorigenesis and tumor progression. Am J Cancer Res. 2011;1:897–912.PubMedCentralPubMedGoogle Scholar
  33. 33.
    Acun T, Oztas E, Yagci T, Yakicier MC. SIP1 is downregulated in hepatocellular carcinoma by promoter hypermethylation. BMC Cancer. 2011;11:223.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Rodenhiser DI, Andrews J, Kennette W, Sadikovic B, Mendlowitz A, Tuck AB, et al. Epigenetic mapping and functional analysis in a breast cancer metastasis model using whole-genome promoter tiling microarrays. Breast Cancer Res. 2008;10:R62.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Li A, Omura N, Hong SM, Vincent A, Walter K, Griffith M, et al. Pancreatic cancers epigenetically silence SIP1 and hypomethylate and overexpress miR-200a/200b in association with elevated circulating miR-200a and miR-200b levels. Cancer Res. 2010;70:5226–37.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A, et al. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol. 2009;11:1487–95.PubMedCrossRefGoogle Scholar
  37. 37.
    Hosono S, Kajiyama H, Terauchi M, Shibata K, Ino K, Nawa A, et al. Expression of Twist increases the risk for recurrence and for poor survival in epithelial ovarian carcinoma patients. Br J Cancer. 2007;96:314–20.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Niu RF, Zhang L, Xi GM, Wei XY, Yang Y, Shi YR, et al. Upregulation of Twist induces angiogenesis and correlates with metastasis in hepatocellular carcinoma. J Exp Clin Cancer Res. 2007;26:385–94.PubMedGoogle Scholar
  39. 39.
    Luo GQ, Li JH, Wen JF, Zhou YH, Hu YB, Zhou JH. Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells. World J Gastroenterol. 2008;14:2487–93.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Yuen HF, Chan YP, Wong ML, Kwok WK, Chan KK, Lee PY, et al. Upregulation of Twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis. J Clin Pathol. 2007;60:510–4.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Song LB, Liao WT, Mai HQ, Zhang HZ, Zhang L, Li MZ, et al. The clinical significance of twist expression in nasopharyngeal carcinoma. Cancer Lett. 2006;242:258–65.PubMedCrossRefGoogle Scholar
  42. 42.
    Yuen HF, Chua CW, Chan YP, Wong YC, Wang X, Chan KW. Significance of TWIST and E-cadherin expression in the metastatic progression of prostatic cancer. Histopathology. 2007;50:648–58.PubMedCrossRefGoogle Scholar
  43. 43.
    McConkey DJ, Choi W, Marquis L, Martin F, Williams MB, Shah J, et al. Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer. Cancer Metastasis Rev. 2009;28:335–44.PubMedCrossRefGoogle Scholar
  44. 44.
    Elias MC, Tozer KR, Silber JR, Mikheeva S, Deng M, Morrison RS, et al. TWIST is expressed in human gliomas and promotes invasion. Neoplasia. 2005;7:824–37.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Ou DL, Chien HF, Chen CL, Lin TC, Lin LI. Role of Twist in head and neck carcinoma with lymph node metastasis. Anticancer Res. 2008;28:1355–9.PubMedGoogle Scholar
  46. 46.
    Salerno P, Garcia-Rostan G, Piccinin S, Bencivenga TC, Di Maro G, Doglioni C, et al. TWIST1 plays a pleiotropic role in determining the anaplastic thyroid cancer phenotype. J Clin Endocrinol Metab. 2011;96:E772–81.PubMedCrossRefGoogle Scholar
  47. 47.
    Singh S, Mak IW, Cowan RW, Turcotte R, Singh G, Ghert M. The role of TWIST as a regulator in giant cell tumor of bone. J Cell Biochem. 2011;112:2287–95.PubMedCrossRefGoogle Scholar
  48. 48.
    Huang KT, Dobrovic A, Yan M, Karim RZ, Lee CS, Lakhani SR, et al. DNA methylation profiling of phyllodes and fibroadenoma tumours of the breast. Breast Cancer Res Treat. 2010;124:555–65.PubMedCrossRefGoogle Scholar
  49. 49.
    Missaoui N, Hmissa S, Trabelsi A, Traoré C, Mokni M, Dante R, et al. Promoter hypermethylation of CDH13, DAPK1 and TWIST1 genes in precancerous and cancerous lesions of the uterine cervix. Pathol Res Pract. 2011;207:37–42.PubMedCrossRefGoogle Scholar
  50. 50.
    Dhillon VS, Aslam M, Husain SA. The contribution of genetic and epigenetic changes in granulosa cell tumors of ovarian origin. Clin Cancer Res. 2004;10:5537–45.PubMedCrossRefGoogle Scholar
  51. 51.
    Renard I, Joniau S, van Cleynenbreugel B, Collette C, Naômé C, Vlassenbroeck I, et al. Identification and validation of the methylated TWIST1 and NID2 genes through real-time methylation-specific polymerase chain reaction assays for the noninvasive detection of primary bladder cancer in urine samples. Eur Urol. 2010;58:96–104.PubMedCrossRefGoogle Scholar
  52. 52.
    Schneider BG, Peng DF, Camargo MC, Piazuelo MB, Sicinschi LA, Mera R, et al. Promoter DNA hypermethylation in gastric biopsies from subjects at high and low risk for gastric cancer. Int J Cancer. 2010;127:2588–97.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Tsou JA, Galler JS, Siegmund KD, Laird PW, Turla S, Cozen W, et al. Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma. Mol Cancer. 2007;6:70.PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Kwon MJ, Kwon JH, Nam ES, Shin HS, Lee DJ, Kim JH, et al. TWIST1 promoter methylation is associated with prognosis in tonsillar squamous cell carcinoma. Hum Pathol. 2013;44:1722–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Moody SE, Perez D, Pan TC, Sarkisian CJ, Portocarrero CP, Sterner CJ, et al. The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell. 2005;8:197–209.PubMedCrossRefGoogle Scholar
  56. 56.
    Fan F, Samuel S, Evans KW, Lu J, Xia L, Zhou Y, et al. Overexpression of snail induces epithelial-mesenchymal transition and a cancer stem cell-like phenotype in human colorectal cancer cells. Cancer Med. 2012;1:5–16.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Zhu LF, Hu Y, Yang CC, Xu XH, Ning TY, Wang ZL, et al. Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells. Lab Invest. 2012;92:744–52.PubMedCrossRefGoogle Scholar
  58. 58.
    Shin NR, Jeong EH, Choi CI, Moon HJ, Kwon CH, Chu IS, et al. Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer. BMC Cancer. 2012;12:521.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Kim MK, Kim MA, Kim H, Kim YB, Song YS. Expression profiles of epithelial-mesenchymal transition-associated proteins in epithelial ovarian carcinoma. Biomed Res Int. 2014;2014:495754.PubMedCentralPubMedGoogle Scholar
  60. 60.
    Roy HK, Smyrk TC, Koetsier J, Victor TA, Wali RK. The transcriptional repressor SNAIL is overexpressed in human colon cancer. Dig Dis Sci. 2005;50:42–6.PubMedCrossRefGoogle Scholar
  61. 61.
    De Craene B, Denecker G, Vermassen P, Taminau J, Mauch C, Derore A, et al. Epidermal Snail expression drives skin cancer initiation and progression through enhanced cytoprotection, epidermal stem/progenitor cell expansion and enhanced metastatic potential. Cell Death Differ. 2014;21:310–20.PubMedCrossRefGoogle Scholar
  62. 62.
    Cai J. Roles of transcriptional factor Snail and adhesion factor E-cadherin in clear cell renal cell carcinoma. Exp Ther Med. 2013;6:1489–93.PubMedCentralPubMedGoogle Scholar
  63. 63.
    Neal CL, Henderson V, Smith BN, McKeithen D, Graham T, Vo BT, et al. Snail transcription factor negatively regulates maspin tumor suppressor in human prostate cancer cells. BMC Cancer. 2012;12:336.PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Castro Alves C, Rosivatz E, Schott C, Hollweck R, Becker I, Sarbia M, et al. Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the down-regulation of E-cadherin. J Pathol. 2007;211:507–15.PubMedCrossRefGoogle Scholar
  65. 65.
    Shih JY, Yang PC. The EMT regulator slug and lung carcinogenesis. Carcinogenesis. 2011;32:1299–304.PubMedCrossRefGoogle Scholar
  66. 66.
    Shioiri M, Shida T, Koda K, Oda K, Seike K, Nishimura M, et al. Slug expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients. Br J Cancer. 2006;94:1816–22.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Yang HW, Menon LG, Black PM, Carroll RS, Johnson MD. SNAI2/Slug promotes growth and invasion in human gliomas. BMC Cancer. 2010;10:301.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Zhang K, Chen D, Jiao X, Zhang S, Liu X, Cao J, et al. Slug enhances invasion ability of pancreatic cancer cells through upregulation of matrix metalloproteinase-9 and actin cytoskeleton remodeling. Lab Invest. 2011;91:426–38.PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Elloul S, Elstrand MB, Nesland JM, Tropé CG, Kvalheim G, Goldberg I, et al. Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma. Cancer. 2005;103:1631–43.PubMedCrossRefGoogle Scholar
  70. 70.
    Uygur B, Wu WS. SLUG promotes prostate cancer cell migration and invasion via CXCR4/CXCL12 axis. Mol Cancer. 2011;10:139.PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Giannelli G, Bergamini C, Fransvea E, Sgarra C, Antonaci S. Laminin-5 with transforming growth factor-beta1 induces epithelial to mesenchymal transition in hepatocellular carcinoma. Gastroenterology. 2005;129:1375–83.PubMedCrossRefGoogle Scholar
  72. 72.
    Spoelstra NS, Manning NG, Higashi Y, Darling D, Singh M, Shroyer KR, et al. The transcription factor ZEB1 is aberrantly expressed in aggressive uterine cancers. Cancer Res. 2006;66:3893–902.PubMedCrossRefGoogle Scholar
  73. 73.
    Spaderna S, Schmalhofer O, Hlubek F, Berx G, Eger A, Merkel S, et al. A transient, EMT-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer. Gastroenterology. 2006;131:830–40.PubMedCrossRefGoogle Scholar
  74. 74.
    Dohadwala M, Yang SC, Luo J, Sharma S, Batra RK, Huang M, et al. Cyclooxygenase-2-dependent regulation of E-cadherin: prostaglandin E(2) induces transcriptional repressors ZEB1 and snail in non-small cell lung cancer. Cancer Res. 2006;66:5338–45.PubMedCrossRefGoogle Scholar
  75. 75.
    Graham TR, Zhau HE, Odero-Marah VA, Osunkoya AO, Kimbro KS, Tighiouart M, et al. Insulin-like growth factor-I-dependent up-regulation of ZEB1 drives epithelial-to-mesenchymal transition in human prostate cancer cells. Cancer Res. 2008;68:2479–88.PubMedCrossRefGoogle Scholar
  76. 76.
    Adachi Y, Takeuchi T, Nagayama T, Ohtsuki Y, Furihata M. Zeb1-mediated T-cadherin repression increases the invasive potential of gallbladder cancer. FEBS Lett. 2009;583:430–6.PubMedCrossRefGoogle Scholar
  77. 77.
    Sayan AE, Griffiths TR, Pal R, Browne GJ, Ruddick A, Yagci T, et al. SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer. Proc Natl Acad Sci U S A. 2009;106:14884–9.PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Celià-Terrassa T, Meca-Cortés O, Mateo F, de Paz AM, Rubio N, Arnal-Estapé A, et al. Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells. J Clin Invest. 2012;122:1849–68.PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Scanlon CS, Van Tubergen EA, Inglehart RC, D’Silva NJ. Biomarkers of epithelial-mesenchymal transition in squamous cell carcinoma. J Dent Res. 2013;92:114–21.PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Zhuo WL, Wang Y, Zhuo XL, Zhang YS, Chen ZT. Short interfering RNA directed against TWIST, a novel zinc finger transcription factor, increases A549 cell sensitivity to cisplatin via MAPK/mitochondrial pathway. Biochem Biophys Res Commun. 2008;369:1098–102.PubMedCrossRefGoogle Scholar
  81. 81.
    Li QQ, Xu JD, Wang WJ, Cao XX, Chen Q, Tang F, et al. Twist1-mediated adriamycin-induced epithelial-mesenchymal transition relates to multidrug resistance and invasive potential in breast cancer cells. Clin Cancer Res. 2009;15:2657–65.PubMedCrossRefGoogle Scholar
  82. 82.
    Weissenberger J, Priester M, Bernreuther C, Rakel S, Glatzel M, Seifert V, et al. Dietary curcumin attenuates glioma growth in a syngeneic mouse model by inhibition of the JAK1,2/STAT3 signaling pathway. Clin Cancer Res. 2010;16:5781–95.PubMedCrossRefGoogle Scholar
  83. 83.
    Srivastava RK, Tang SN, Zhu W, Meeker D, Shankar S. Sulforaphane synergizes with quercetin to inhibit self-renewal capacity of pancreatic cancer stem cells. Front Biosci (Elite Ed). 2011;3:515–28.CrossRefGoogle Scholar
  84. 84.
    Chang WW, Hu FW, Yu CC, Wang HH, Feng HP, Lan C, et al. Quercetin in elimination of tumor initiating stem-like and mesenchymal transformation property in head and neck cancer. Head Neck. 2013;35:413–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Pai HC, Chang LH, Peng CY, Chang YL, Chen CC, Shen CC, et al. Moscatilin inhibits migration and metastasis of human breast cancer MDA-MB-231 cells through inhibition of Akt and Twist signaling pathway. J Mol Med (Berl). 2013;91:347–56.CrossRefGoogle Scholar
  86. 86.
    Khan MA, Yang M, Wei C, Gan L, Fu J. Thymoquinone downregulates n-cadherin, twist and snail expression and inhibits migration and invasion in cancer cells. Proceedings of Annual meeting of American Association of Cancer Research; April 05-09, 2014 at San Diego, USA (Abstract No. 5009).Google Scholar
  87. 87.
    Lin X, Yi Z, Diao J, Shao M, Zhao L, Cai H, et al. ShaoYao decoction ameliorates colitis-associated colorectal cancer by downregulating proinflammatory cytokines and promoting epithelial-mesenchymal transition. J Transl Med. 2014;12:105.PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Huang Y, Liu W, Liu H, Yang Y, Cui J, Zhang P, et al. Grape seed pro-anthocyanidins ameliorates radiation-induced lung injury. J Cell Mol Med. 2014 Apr 24. (in press).Google Scholar
  89. 89.
    Lv M, Li Y, Ji MH, Zhuang M, Tang JH. Inhibition of invasion and epithelial-mesenchymal transition of human breast cancer cells by hydrogen sulfide through decreased phospho-p38 expression. Mol Med Rep. 2014 Apr 17. (in press).Google Scholar
  90. 90.
    Bao B, Azmi A, Aboukameel A, Ahmad A, Bolling-Fischer A, Sethi S, et al. Pancreatic cancer stem-like cells display aggressive behavior mediated via activation of FoxQ1. J Biol Chem. 2014 Apr 9. (in press).Google Scholar
  91. 91.
    Zhang JP, Zeng C, Xu L, Gong J, Fang JH, Zhuang SM. MicroRNA-148a suppresses the epithelial-mesenchymal transition and metastasis of hepatoma cells by targeting Met/Snail signaling. Oncogene. 2013 Sep 9. (in press).Google Scholar
  92. 92.
    Zhao W, Zhou Y, Xu H, Cheng Y, Kong B. Snail family proteins in cervical squamous carcinoma: expression and significance. Clin Invest Med. 2013;36:E223–33.PubMedGoogle Scholar
  93. 93.
    Riemenschnitter C, Teleki I, Tischler V, Guo W, Varga Z. Stability and prognostic value of Slug, Sox9 and Sox10 expression in breast cancers treated with neoadjuvant chemotherapy. Springerplus. 2013;2:695.PubMedCentralPubMedCrossRefGoogle Scholar
  94. 94.
    Lee HJ, Jeng YM, Chen YL, Chung L, Yuan RH. Gas6/Axl pathway promotes tumor invasion through the transcriptional activation of Slug in hepatocellular carcinoma. Carcinogenesis. 2013;35:769–75.PubMedCrossRefGoogle Scholar
  95. 95.
    Ding G, Feng C, Jiang H, Ding Q, Zhang L, Na R, et al. Combination of rapamycin, CI-1040, and 17-AAG inhibits metastatic capacity of prostate cancer via Slug inhibition. PLoS One. 2013;8:e77400.PubMedCentralPubMedCrossRefGoogle Scholar
  96. 96.
    Piva R, Spandidos DA, Gambari R. From microRNA functions to microRNA therapeutics: novel targets and novel drugs in breast cancer research and treatment (Review). Int J Oncol. 2013;43:985–94.PubMedCentralPubMedGoogle Scholar
  97. 97.
    Qian J, Liu H, Chen W, Wen K, Lu W, Huang C, et al. Knockdown of Slug by RNAi inhibits the proliferation and invasion of HCT116 colorectal cancer cells. Mol Med Rep. 2013;8:1055–9.PubMedGoogle Scholar
  98. 98.
    Wang YP, Wang MZ, Luo YR, Shen Y, Wei ZX. Lentivirus-mediated shRNA interference targeting SLUG inhibits lung cancer growth and metastasis. Asian Pac J Cancer Prev. 2012;13:4947–51.PubMedCrossRefGoogle Scholar
  99. 99.
    Liu Y, Yan X, Liu N, Zhou J, Liu J, Pang H, et al. Lentivirus-delivered ZEB-1 small interfering RNA inhibits lung adenocarcinoma cell growth in vitro and in vivo. J Cancer Res Clin Oncol. 2012;138:1329–38.PubMedCrossRefGoogle Scholar
  100. 100.
    Arima Y, Hayashi H, Sasaki M, Hosonaga M, Goto TM, Chiyoda T, et al. Induction of ZEB proteins by inactivation of RB protein is key determinant of mesenchymal phenotype of breast cancer. J Biol Chem. 2012;287:7896–906.PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Shen A, Zhang Y, Yang H, Xu R, Huang G. Overexpression of ZEB1 relates to metastasis and invasion in osteosarcoma. J Surg Oncol. 2012;105:830–4.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Mousumi Tania
    • 1
  • Md. Asaduzzaman Khan
    • 1
  • Junjiang Fu
    • 1
  1. 1.Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical MedicineLuzhou Medical CollegeLuzhouChina

Personalised recommendations