Tumor Biology

, Volume 37, Issue 2, pp 1531–1539 | Cite as

Research advances in HMGN5 and cancer

Review

Abstract

High-mobility group nucleosome-binding domain 5 (HMGN5) is a new member of the high-mobility group N (HMGN) protein family that is involved in nucleosomal binding and transcriptional activation. It was first discovered in mouse, and recent studies found that the expressions of HMGN5 in many human cancers were also highly regulated, such as prostate, bladder, breast, and lung and clear cell renal cell carcinoma. Numerous reports have demonstrated that HMGN5 plays significant roles in many biological and pathological conditions, such as in developmental defects, hypersensitivity to stress, embryonic stem cell differentiation, and tumor progression. Importantly, deficiency of HMGN5 has been shown to be linked to cancer cell growth, cell cycle regulation, migration, invasion, and clinical outcomes, and it represents a promising therapeutic target for many malignant tumors. In the present review, we provide an overview of the current knowledge concerning the role of HMGN5 in cancer development and progression.

Keywords

High-mobility group protein nucleosome-binding domain 5 Cancer Metastasis Autophagy Apoptosis 

Notes

Compliance with ethical standards

Conflicts of interest

None

References

  1. 1.
    Hock R, Furusawa T, Ueda T, Bustin M. HMG chromosomal proteins in development and disease. Trends Cell Biol. 2007;17(2):72–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Postnikov Y, Bustin M. Regulation of chromatin structure and function by HMGN proteins. Biochim Biophys Acta. 2010;1799(1–2):62–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Rochman M, Taher L, Kurahashi T, Cherukuri S, Uversky VN, Landsman D, et al. Effects of HMGN variants on the cellular transcription profile. Nucleic Acids Res. 2011;39(10):4076–87.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Kugler JE, Deng T, Bustin M. The HMGN family of chromatin-binding proteins: dynamic modulators of epigenetic processes. Biochim Biophys Acta. 2012;1819(7):652–6.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Furusawa T, Cherukuri S. Developmental function of HMGN proteins. Biochim Biophys Acta. 2010;1799(1–2):69–73.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Rochman M, Malicet C, Bustin M. HMGN5/NSBP1: a new member of the HMGN protein family that affects chromatin structure and function. Biochim Biophys Acta. 2010;1799(1–2):86–92.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Rochman M, Postnikov Y, Correll S, Malicet C, Wincovitch S, Karpova TS, et al. The interaction of NSBP1/HMGN5 with nucleosomes in euchromatin counteracts linker histone-mediated chromatin compaction and modulates transcription. Mol Cell. 2009;35(5):642–56.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Shirakawa H, Landsman D, Postnikov YV, Bustin M. NBP-45, a novel nucleosomal binding protein with a tissue-specific and developmentally regulated expression. J Biol Chem. 2000;275(9):6368–74.CrossRefPubMedGoogle Scholar
  9. 9.
    King LM, Francomano CA. Characterization of a human gene encoding nucleosomal binding protein NSBP1. Genomics. 2001;71(2):163–73.CrossRefPubMedGoogle Scholar
  10. 10.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.CrossRefPubMedGoogle Scholar
  11. 11.
    Song G, Zhou LQ, Weng M, He Q, He ZS, Hao JR, et al. Expression of nucleosomal binding protein 1 in normal prostate benign prostate hyperplasia, and prostate cancer and significance thereof. Zhonghua Yi Xue Za Zhi. 2006;86(28):1962–5.PubMedGoogle Scholar
  12. 12.
    Jiang N, Zhou LQ, Zhang XY. Downregulation of the nucleosome-binding protein 1 (NSBP1) gene can inhibit the in vitro and in vivo proliferation of prostate cancer cells. Asian J Androl. 2010;12(5):709–17.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Zhang XY, Guo ZQ, Ji SQ, Zhang M, Jiang N, Li XS, et al. Small interfering RNA targeting HMGN5 induces apoptosis via modulation of a mitochondrial pathway and Bcl-2 family proteins in prostate cancer cells. Asian J Androl. 2012;14(3):487–92.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Su B, Shi B, Tang Y, Guo Z, Yu X, He X, et al. HMGN5 knockdown sensitizes prostate cancer cells to ionizing radiation. Prostate. 2015;75(1):33–44.CrossRefPubMedGoogle Scholar
  15. 15.
    Huang CY, Chang YJ, Luo SD, Uyanga B, Lin FY, Tai CJ et al. Maspin mediates the gemcitabine sensitivity of hormone-independent prostate cancer. Tumour Biol J Int Soc Oncodev Biol Med. 2015. doi: 10.1007/s13277-015-4083-x.
  16. 16.
    Guo Z, Zhang X, Li X, Xie F, Su B, Zhang M, et al. Expression of oncogenic HMGN5 increases the sensitivity of prostate cancer cells to gemcitabine. Oncol Rep. 2015;33(3):1519–25.PubMedGoogle Scholar
  17. 17.
    Wei P, Qiao B, Li Q, Han X, Zhang H, Huo Q, et al. microRNA-340 suppresses tumorigenic potential of prostate cancer cells by targeting high-mobility group nucleosome-binding domain 5. DNA Cell Biol. 2015. doi: 10.1089/dna.2015.3021.
  18. 18.
    Wahafu W, He ZS, Zhang XY, Zhang CJ, Yao K, Hao H, et al. The nucleosome binding protein NSBP1 is highly expressed in human bladder cancer and promotes the proliferation and invasion of bladder cancer cells. Tumour Biol J Int Soc Oncodev Biol Med. 2011;32(5):931–9.CrossRefGoogle Scholar
  19. 19.
    Gan Y, Tan J, Yang J, Zhou Y, Dai Y, He L, et al. Knockdown of HMGN5 suppresses the viability and invasion of human urothelial bladder cancer 5637 cells in vitro and in vivo. Med Oncol. 2015;32(4):136.CrossRefPubMedGoogle Scholar
  20. 20.
    Yao K, He L, Gan Y, Zeng Q, Dai Y, Tan J. MiR-186 suppresses the growth and metastasis of bladder cancer by targeting NSBP1. Diagn Pathol. 2015;10:146.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Zhao Z, Wu F, Ding S, Sun L, Liu Z, Ding K, et al. Label-free quantitative proteomic analysis reveals potential biomarkers and pathways in renal cell carcinoma. Tumour Biol J Int Soc Oncodev Biol Med. 2015;36(2):939–51.CrossRefGoogle Scholar
  22. 22.
    Brugarolas J. Molecular genetics of clear-cell renal cell carcinoma. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32(18):1968–76.CrossRefGoogle Scholar
  23. 23.
    Ji SQ, Yao L, Zhang XY, Li XS, Zhou LQ. Knockdown of the nucleosome binding protein 1 inhibits the growth and invasion of clear cell renal cell carcinoma cells in vitro and in vivo. J Exp Clin Cancer Res. 2012;31:22.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Chen P, Wang XL, Ma ZS, Xu Z, Jia B, Ren J, et al. Knockdown of HMGN5 expression by RNA interference induces cell cycle arrest in human lung cancer cells. Asian Pac J Cancer Prev. 2012;13(7):3223–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Li DQ, Hou YF, Wu J, Chen Y, Lu JS, Di GH, et al. Gene expression profile analysis of an isogenic tumour metastasis model reveals a functional role for oncogene AF1Q in breast cancer metastasis. Eur J Cancer. 2006;42(18):3274–86.CrossRefPubMedGoogle Scholar
  26. 26.
    Weng M, Song F, Chen J, Wu J, Qin J, Jin T, et al. The high-mobility group nucleosome-binding domain 5 is highly expressed in breast cancer and promotes the proliferation and invasion of breast cancer cells. Tumour Biol J Int Soc Oncodev Biol Med. 2015;36(2):959–66.CrossRefGoogle Scholar
  27. 27.
    Moore DD, Luu HH. Osteosarcoma. Cancer Treat Res. 2014;162:65–92.CrossRefPubMedGoogle Scholar
  28. 28.
    Zhou X, Yuan B, Yuan W, Wang C, Gao R, Wang J. The expression and clinical significance of high mobility group nucleosome binding domain 5 in human osteosarcoma. Tumour Biol J Int Soc Oncodev Biol Med. 2014;35(7):6539–47.CrossRefGoogle Scholar
  29. 29.
    Zhou W, Hao M, Du X, Chen K, Wang G, Yang J. Advances in targeted therapy for osteosarcoma. Discov Med. 2014;17(96):301–7.PubMedGoogle Scholar
  30. 30.
    Desandes E. Survival from adolescent cancer. Cancer Treat Rev. 2007;33(7):609–15.CrossRefPubMedGoogle Scholar
  31. 31.
    Xiao X, Wang W, Wang Z. The role of chemotherapy for metastatic, relapsed and refractory osteosarcoma. Paediatr Drugs. 2014;16(6):503–12.CrossRefPubMedGoogle Scholar
  32. 32.
    Yang C, Gao R, Wang J, Yuan W, Wang C, Zhou X. High-mobility group nucleosome-binding domain 5 increases drug resistance in osteosarcoma through upregulating autophagy. Tumour Biol J Int Soc Oncodev Biol Med. 2014;35(7):6357–63.CrossRefGoogle Scholar
  33. 33.
    Qu J, Yan R, Chen J, Xu T, Zhou J, Wang M, et al. HMGN5: a potential oncogene in gliomas. J Neuro-Oncol. 2011;104(3):729–36.CrossRefGoogle Scholar
  34. 34.
    Tsai JH, Yang J. Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev. 2013;27(20):2192–206.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Spano D, Heck C, De Antonellis P, Christofori G, Zollo M. Molecular networks that regulate cancer metastasis. Semin Cancer Biol. 2012;22(3):234–49.CrossRefPubMedGoogle Scholar
  36. 36.
    Su Z, Yang Z, Xu Y, Chen Y, Yu Q. Apoptosis, autophagy, necroptosis, and cancer metastasis. Mol Cancer. 2015;14:48.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Acloque H, Adams MS, Fishwick K, Bronner-Fraser M, Nieto MA. Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest. 2009;119(6):1438–49.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15(3):178–96.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Cao H, Xu E, Liu H, Wan L, Lai M. Epithelial-mesenchymal transition in colorectal cancer metastasis: a system review. Pathol Res Pract. 2015;211(8):557–69.CrossRefPubMedGoogle Scholar
  40. 40.
    Wong IY, Javaid S, Wong EA, Perk S, Haber DA, Toner M, et al. Collective and individual migration following the epithelial-mesenchymal transition. Nat Mater. 2014;13(11):1063–71.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Yilmaz M, Christofori G. EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 2009;28(1–2):15–33.CrossRefPubMedGoogle Scholar
  42. 42.
    Garg M. Targeting microRNAs in epithelial-to-mesenchymal transition-induced cancer stem cells: therapeutic approaches in cancer. Expert Opin Ther Targets. 2015;19(2):285–97.CrossRefPubMedGoogle Scholar
  43. 43.
    Zaravinos A. The regulatory role of microRNAs in EMT and cancer. J Oncol. 2015;2015:865816.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Yun SJ, Kim WJ. Role of the epithelial-mesenchymal transition in bladder cancer: from prognosis to therapeutic target. Korean J Urol. 2013;54(10):645–50.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Xiong D, Liou Y, Shu J, Li D, Zhang L, Chen J. Down-regulating ribonuclease inhibitor enhances metastasis of bladder cancer cells through regulating epithelial-mesenchymal transition and ILK signaling pathway. Exp Mol Pathol. 2014;96(3):411–21.CrossRefPubMedGoogle Scholar
  46. 46.
    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(3–4):335–44.CrossRefPubMedGoogle Scholar
  47. 47.
    Wheelock MJ, Shintani Y, Maeda M, Fukumoto Y, Johnson KR. Cadherin switching. J Cell Sci. 2008;121(Pt 6):727–35.CrossRefPubMedGoogle Scholar
  48. 48.
    Jeanes A, Gottardi CJ, Yap AS. Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene. 2008;27(55):6920–9.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Stemmler MP. Cadherins in development and cancer. Mol BioSyst. 2008;4(8):835–50.CrossRefPubMedGoogle Scholar
  50. 50.
    Bryan RT, Tselepis C. Cadherin switching and bladder cancer. J Urol. 2010;184(2):423–31.CrossRefPubMedGoogle Scholar
  51. 51.
    Roy R, Yang J, Moses MA. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2009;27(31):5287–97.CrossRefGoogle Scholar
  52. 52.
    Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010;141(1):52–67.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002;2(3):161–74.CrossRefPubMedGoogle Scholar
  54. 54.
    Yen JH, Kocieda VP, Jing H, Ganea D. Prostaglandin E2 induces matrix metalloproteinase 9 expression in dendritic cells through two independent signaling pathways leading to activator protein 1 (AP-1) activation. J Biol Chem. 2011;286(45):38913–23.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Murphy DA, Courtneidge SA. The ‘ins’ and ‘outs’ of podosomes and invadopodia: characteristics, formation and function. Nat Rev Mol Cell Biol. 2011;12(7):413–26.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Moroz A, Delella FK, Almeida R, Lacorte LM, Favaro WJ, Deffune E, et al. Finasteride inhibits human prostate cancer cell invasion through MMP2 and MMP9 downregulation. PLoS One. 2013;8(12):e84757.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Yan Y, Liang H, Li T, Li M, Li R, Qin X, et al. The MMP-1, MMP-2, and MMP-9 gene polymorphisms and susceptibility to bladder cancer: a meta-analysis. Tumour Biol J Int Soc Oncodev Biol Med. 2014;35(4):3047–52.CrossRefGoogle Scholar
  58. 58.
    Lu H, Cao X, Zhang H, Sun G, Fan G, Chen L, et al. Imbalance between MMP-2, 9 and TIMP-1 promote the invasion and metastasis of renal cell carcinoma via SKP2 signaling pathways. Tumour Biol J Int Soc Oncodev Biol Med. 2014;35(10):9807–13.CrossRefGoogle Scholar
  59. 59.
    Yang J, Kuang XR, Lv PT, Yan XX. Thymoquinone inhibits proliferation and invasion of human nonsmall-cell lung cancer cells via ERK pathway. Tumour Biol J Int Soc Oncodev Biol Med. 2015;36(1):259–69.CrossRefGoogle Scholar
  60. 60.
    Zhang Y, Pan T, Zhong X, Cheng C. Androgen receptor promotes esophageal cancer cell migration and proliferation via matrix metalloproteinase 2. Tumour Biol J Int Soc Oncodev Biol Med. 2015;36(8):5859–64.CrossRefGoogle Scholar
  61. 61.
    Zhang MX, Xu XM, Zhang P, Han NN, Deng JJ, Yu TT, et al. Effect of silencing NEK2 on biological behaviors of HepG2 in human hepatoma cells and MAPK signal pathway. Tumour Biol J Int Soc Oncodev Biol Med. 2015. doi: 10.1007/s13277-015-3993-y.
  62. 62.
    Ganguly K, Rejmak E, Mikosz M, Nikolaev E, Knapska E, Kaczmarek L. Matrix metalloproteinase (MMP) 9 transcription in mouse brain induced by fear learning. J Biol Chem. 2013;288(29):20978–91.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Liu SJ, Yin CX, Ding MC, Xia SY, Shen QM, Wu JD. Berberine suppresses in vitro migration of human aortic smooth muscle cells through the inhibitions of MMP-2/9, u-PA, AP-1, and NF-kappaB. BMB Rep. 2014;47(7):388–92.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Yoo SY, Kwon SM. Angiogenesis and its therapeutic opportunities. Mediat Inflamm. 2013;2013:127170.CrossRefGoogle Scholar
  65. 65.
    Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011;473(7347):298–307.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Jain RK. Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. Cancer Cell. 2014;26(5):605–22.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Moens S, Goveia J, Stapor PC, Cantelmo AR, Carmeliet P. The multifaceted activity of VEGF in angiogenesis—implications for therapy responses. Cytokine Growth Factor Rev. 2014;25(4):473–82.CrossRefPubMedGoogle Scholar
  68. 68.
    Liang X, Xu F, Li X, Ma C, Zhang Y, Xu W. VEGF signal system: the application of antiangiogenesis. Curr Med Chem. 2014;21(7):894–910.CrossRefPubMedGoogle Scholar
  69. 69.
    Cook KM, Figg WD. Angiogenesis inhibitors: current strategies and future prospects. CA Cancer J Clin. 2010;60(4):222–43.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Le Bras B, Barallobre MJ, Homman-Ludiye J, Ny A, Wyns S, Tammela T, et al. VEGF-C is a trophic factor for neural progenitors in the vertebrate embryonic brain. Nat Neurosci. 2006;9(3):340–8.CrossRefPubMedGoogle Scholar
  71. 71.
    Xu H, Zhang T, Man GC, May KE, Becker CM, Davis TN, et al. Vascular endothelial growth factor C is increased in endometrium and promotes endothelial functions, vascular permeability and angiogenesis and growth of endometriosis. Angiogenesis. 2013;16(3):541–51.CrossRefPubMedGoogle Scholar
  72. 72.
    Alitalo A, Detmar M. Interaction of tumor cells and lymphatic vessels in cancer progression. Oncogene. 2012;31(42):4499–508.CrossRefPubMedGoogle Scholar
  73. 73.
    Kondo Y, Kanzawa T, Sawaya R, Kondo S. The role of autophagy in cancer development and response to therapy. Nat Rev Cancer. 2005;5(9):726–34.CrossRefPubMedGoogle Scholar
  74. 74.
    Amaravadi RK, Lippincott-Schwartz J, Yin XM, Weiss WA, Takebe N, Timmer W, et al. Principles and current strategies for targeting autophagy for cancer treatment. Clin Cancer Res Off J Am Assoc Cancer Res. 2011;17(4):654–66.CrossRefGoogle Scholar
  75. 75.
    Valente G, Morani F. Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer. BioMed Res Int. 2014. doi: 10.1155/2014/462658.
  76. 76.
    Sun Y, Liu JH, Jin L, Lin SM, Yang Y, Sui YX, et al. Over-expression of the Beclin1 gene upregulates chemosensitivity to anti-cancer drugs by enhancing therapy-induced apoptosis in cervix squamous carcinoma CaSki cells. Cancer Lett. 2010;294(2):204–10.CrossRefPubMedGoogle Scholar
  77. 77.
    Huang R, Liu W. Identifying an essential role of nuclear LC3 for autophagy. Autophagy. 2015;11(5):852–3.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Randhawa R, Sehgal M, Singh TR, Duseja A, Changotra H. Unc-51 like kinase 1 (ULK1) in silico analysis for biomarker identification: a vital component of autophagy. Gene. 2015;562(1):40–9.CrossRefPubMedGoogle Scholar
  79. 79.
    Fan YJ, Zong WX. The cellular decision between apoptosis and autophagy. Chin J Cancer. 2013;32(3):121–9.PubMedPubMedCentralGoogle Scholar
  80. 80.
    El-Khattouti A, Selimovic D, Haikel Y, Hassan M. Crosstalk between apoptosis and autophagy: molecular mechanisms and therapeutic strategies in cancer. J Cell Death. 2013;6:37–55.PubMedPubMedCentralGoogle Scholar
  81. 81.
    Kang MH, Reynolds CP. Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy. Clin Cancer Res Off J Am Assoc Cancer Res. 2009;15(4):1126–32.CrossRefGoogle Scholar
  82. 82.
    Juraver-Geslin HA, Durand BC. Early development of the neural plate: new roles for apoptosis and for one of its main effectors caspase-3. Genesis (New York, NY: 2000). 2015;53(2):203–24.CrossRefGoogle Scholar
  83. 83.
    Gao L, Nieters A, Brenner H. Cell proliferation-related genetic polymorphisms and gastric cancer risk: systematic review and meta-analysis. Eur J Hum Genet. 2009;17(12):1658–67.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    De Falco M, De Luca A. Cell cycle as a target of antineoplastic drugs. Curr Pharm Des. 2010;16(12):1417–26.CrossRefPubMedGoogle Scholar
  85. 85.
    Blomme J, Inze D, Gonzalez N. The cell-cycle interactome: a source of growth regulators? J Exp Bot. 2014;65(10):2715–30.CrossRefPubMedGoogle Scholar
  86. 86.
    Liang S, Mu K, Wang Y, Zhou Z, Zhang J, Sheng Y, et al. CyclinD1, a prominent prognostic marker for endometrial diseases. Diagn Pathol. 2013;8:138.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Qu DW, Xu HS, Han XJ, Wang YL, Ouyang CJ. Expression of cyclinD1 and Ki-67 proteins in gliomas and its clinical significance. Eur Rev Med Pharmacol Sci. 2014;18(4):516–9.PubMedGoogle Scholar
  88. 88.
    Gavet O, Pines J. Progressive activation of CyclinB1-Cdk1 coordinates entry to mitosis. Dev Cell. 2010;18(4):533–43.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Feng W, Cai D, Zhang B, Lou G, Zou X. Combination of HDAC inhibitor TSA and silibinin induces cell cycle arrest and apoptosis by targeting survivin and cyclinB1/Cdk1 in pancreatic cancer cells. Biomed Pharmacother. 2015;74:257–64.CrossRefPubMedGoogle Scholar
  90. 90.
    Wolf F, Wandke C, Isenberg N, Geley S. Dose-dependent effects of stable cyclin B1 on progression through mitosis in human cells. EMBO J. 2006;25(12):2802–13.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 2009;9(8):550–62.CrossRefPubMedGoogle Scholar
  92. 92.
    Dong Y, Liang G, Yuan B, Yang C, Gao R, Zhou X. MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway. Tumour Biol J Int Soc Oncodev Biol Med. 2015;36(3):1477–86.CrossRefGoogle Scholar
  93. 93.
    Zhang L, Wang H, Zhu J, Ding K, Xu J. FTY720 reduces migration and invasion of human glioblastoma cell lines via inhibiting the PI3K/AKT/mTOR/p70S6K signaling pathway. Tumour Biol J Int Soc Oncodev Biol Med. 2014;35(11):10707–14.CrossRefGoogle Scholar
  94. 94.
    Zhen Y, Ye Y, Yu X, Mai C, Zhou Y, Chen Y, et al. Reduced CTGF expression promotes cell growth, migration, and invasion in nasopharyngeal carcinoma. PLoS One. 2014;8(6):e64976.CrossRefPubMedGoogle Scholar
  95. 95.
    Reddy KB, Nabha SM, Atanaskova N. Role of MAP kinase in tumor progression and invasion. Cancer Metastasis Rev. 2003;22(4):395–403.CrossRefPubMedGoogle Scholar
  96. 96.
    Krueger JS, Keshamouni VG, Atanaskova N, Reddy KB. Temporal and quantitative regulation of mitogen-activated protein kinase (MAPK) modulates cell motility and invasion. Oncogene. 2001;20(31):4209–18.CrossRefPubMedGoogle Scholar
  97. 97.
    Zhang T, Yang D, Fan Y, Xie P, Li H. Epigallocatechin-3-gallate enhances ischemia/reperfusion-induced apoptosis in human umbilical vein endothelial cells via AKT and MAPK pathways. Apoptosis Int J Programmed Cell Death. 2009;14(10):1245–54.CrossRefGoogle Scholar
  98. 98.
    Caceres LC, Bonacci GR, Sanchez MC, Chiabrando GA. Activated alpha(2) macroglobulin induces matrix metalloproteinase 9 expression by low-density lipoprotein receptor-related protein 1 through MAPK-ERK1/2 and NF-kappaB activation in macrophage-derived cell lines. J Cell Biochem. 2010;111(3):607–17.CrossRefPubMedGoogle Scholar
  99. 99.
    Xu T, Wang NS, Fu LL, Ye CY, Yu SQ, Mei CL. Celecoxib inhibits growth of human autosomal dominant polycystic kidney cyst-lining epithelial cells through the VEGF/Raf/MAPK/ERK signaling pathway. Mol Biol Rep. 2012;39(7):7743–53.CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Elsum IA, Martin C, Humbert PO. Scribble regulates an EMT polarity pathway through modulation of MAPK-ERK signaling to mediate junction formation. J Cell Sci. 2013;126(Pt 17):3990–9.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of UrologyThe Affiliated Hospital of Xuzhou Medical CollegeXuzhouPeople’s Republic of China

Personalised recommendations