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Article

Histone deacetylase 4 increases progressive epithelial ovarian cancer cells via repression of p21 on fibrillar collagen matrices

  • Authors:
    • Yu-Fei Shen
    • Ai-Min Wei
    • Qing Kou
    • Qiao-Ying Zhu
    • Lei Zhang
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Reproductive Medicine, Department of Gynecology and Obstetrics, Nanjing Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Nanjing 210029, P.R. China
  • Pages: 948-954
    |
    Published online on: November 16, 2015
       https://doi.org/10.3892/or.2015.4423
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Abstract

Histone deacetylase (HDAC) 4 is an emerging target in cancer therapeutics, but little is known about the function of HDAC4 in gynecologic malignancies. Therefore we investigated the mechanism of HDAC4 promoting the proliferation of epithelial ovarian cancer cells (OV). In this study, we observed that the proliferation of cells with HDAC4 inhibitor Trichostatin A (TSA) treatment was markedly decreased, Further, we showed that epithelial ovarian cancer tissues with stage III/IV had higher HDAC4 expression, compared to that with stage I/II. We examined first that the HDAC4 expression was increased in response to fibrillar collagen matrices. In addition, we found that HDAC4 was retained in the nucleus by regulation of PP1α, which regulated HDAC4 cellular fraction via phosphorylation of HDAC4. In addition, we found that HDAC4 bound to Sp1 in epithelial ovarian cancer cells. Finally, ovarian cancer cell line OVCAR3 was evaluated via gain/loss-of-function of HDAC4 by either overexpression of HDCA4 or knock-down of HDAC4 with shRNA. We examined both protein and mRNA of p21 by western blotting and qPCR. We performed analysis of colony formation in matrigel and migration by ECIS. Our results suggest that the accumulation of HDAC4 induced by fibrillar collagen matrices in the nucleus via co-localization of PP1α, leads to repression of the mRNA/protein of p21 and in turn promotes the proliferation and migration of epithelial ovarian cancer cells.
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View References

1 

Engel J, Eckel R, Schubert-Fritschle G, Kerr J, Kuhn W, Diebold J, Kimmig R, Rehbock J and Hölzel D: Moderate progress for ovarian cancer in the last 20 years: Prolongation of survival, but no improvement in the cure rate. Eur J Cancer. 38:2435–2445. 2002. View Article : Google Scholar : PubMed/NCBI

2 

van der Burg ME: Advanced ovarian cancer. Curr Treat Options Oncol. 2:109–118. 2001. View Article : Google Scholar

3 

Watanabe T: Investigational histone deacetylase inhibitors for non-Hodgkin lymphomas. Expert Opin Investig Drugs. 19:1113–1127. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Horwitz SM: The emerging role of histone deacetylase inhibitors in treating T-cell lymphomas. Curr Hematol Malig Rep. 6:67–72. 2011. View Article : Google Scholar

5 

Modesitt SC and Parsons SJ: In vitro and in vivo histone deacetylase inhibitor therapy with vorinostat and paclitaxel in ovarian cancer models: Does timing matter? Gynecol Oncol. 119:351–357. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Egger G, Liang G, Aparicio A and Jones PA: Epigenetics in human disease and prospects for epigenetic therapy. Nature. 429:457–463. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Jones PA and Baylin SB: The fundamental role of epigenetic events in cancer. Nat Rev Genet. 3:415–428. 2002.PubMed/NCBI

8 

Jones PA and Baylin SB: The epigenomics of cancer. Cell. 128:683–692. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Baylin SB and Ohm JE: Epigenetic gene silencing in cancer -a mechanism for early oncogenic pathway addiction? Nat Rev Cancer. 6:107–116. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Takai N, Desmond JC, Kumagai T, Gui D, Said JW, Whittaker S, Miyakawa I and Koeffler HP: Histone deacetylase inhibitors have a profound antigrowth activity in endometrial cancer cells. Clin Cancer Res. 10:1141–1149. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Takai N, Kawamata N, Gui D, Said JW, Miyakawa I and Koeffler HP: Human ovarian carcinoma cells: Histone deacetylase inhibitors exhibit antiproliferative activity and potently induce apoptosis. Cancer. 101:2760–2770. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Timmermann S, Lehrmann H, Polesskaya A and Harel-Bellan A: Histone acetylation and disease. Cell Mol Life Sci. 58:728–736. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Murdoch WJ: Ovarian surface epithelium, ovulation and carcinogenesis. Biol Rev Camb Philos Soc. 71:529–543. 1996. View Article : Google Scholar : PubMed/NCBI

14 

Agarwal R and Kaye SB: Ovarian cancer: Strategies for overcoming resistance to chemotherapy. Nat Rev Cancer. 3:502–516. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Hayashi A, Horiuchi A, Kikuchi N, Hayashi T, Fuseya C, Suzuki A, Konishi I and Shiozawa T: Type-specific roles of histone deacetylase (HDAC) overexpression in ovarian carcinoma: HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with downregulation of E-cadherin. Int J Cancer. 127:1332–1346. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Weichert W, Denkert C, Noske A, Darb-Esfahani S, Dietel M, Kalloger SE, Huntsman DG and Köbel M: Expression of class I histone deacetylases indicates poor prognosis in endometrioid subtypes of ovarian and endometrial carcinomas. Neoplasia. 10:1021–1027. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Shen Y, Shen R, Ge L, Zhu Q and Li F: Fibrillar type I collagen matrices enhance metastasis/invasion of ovarian epithelial cancer via β1 integrin and PTEN signals. Int J Gynecol Cancer. 22:1316–1324. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Isaacs JT, Antony L, Dalrymple SL, Brennen WN, Gerber S, Hammers H, Wissing M, Kachhap S, Luo J, Xing L, et al: Tasquinimod is an allosteric modulator of HDAC4 survival signaling within the compromised cancer microenvironment. Cancer Res. 73:1386–1899. 2013. View Article : Google Scholar :

19 

Geng H, Harvey CT, Pittsenbarger J, Liu Q, Beer TM, Xue C and Qian DZ: HDAC4 protein regulates HIF1α protein lysine acetylation and cancer cell response to hypoxia. J Biol Chem. 286:38095–38102. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Paroni G, Cernotta N, Dello Russo C, Gallinari P, Pallaoro M, Foti C, Talamo F, Orsatti L, Steinkühler C and Brancolini C: PP2A regulates HDAC4 nuclear import. Biol Cell. 19:655–667. 2008.

21 

Perry RLS, Yang C, Soora N, Salma J, Marback M, Naghibi L, Ilyas H, Chan J, Gordon JW and McDermott JC: Direct interaction between myocyte enhancer factor 2 (MEF2) and protein phosphatase 1α represses MEF2-dependent gene expression. Mol Cell Biol. 29:3355–3366. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Liu Y, Randall W and Schneider MF: Activity-dependent and -independent nuclear fluxes of HDAC4 mediated by different kinases in adult skeletal muscle. J Chem Biol. 168:887–897. 2005.

23 

Li J, Chen J, Ricupero CL, Hart RP, Schwartz MS, Kusnecov A and Herrup K: Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia. Nat Med. 18:783–790. 2012. View Article : Google Scholar : PubMed/NCBI

24 

O'Mahony J and Hill C: A real time PCR assay for the detection and quantitation of Mycobacterium avium subsp. paratuberculosis using SYBR Green and the Light Cycler. J Microbiol Methods. 51:283–293. 2002. View Article : Google Scholar : PubMed/NCBI

25 

Krusche CA, Vloet AJ, Classen-Linke I, von Rango U, Beier HM and Alfer J: Class I histone deacetylase expression in the human cyclic endometrium and endometrial adenocarcinomas. Hum Reprod. 22:2956–2966. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Weichert W, Röske A, Gekeler V, Beckers T, Ebert MP, Pross M, Dietel M, Denkert C and Röcken C: Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: A retrospective analysis. Lancet Oncol. 9:139–148. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Ozdağ H, Teschendorff AE, Ahmed AA, Hyland SJ, Blenkiron C, Bobrow L, Veerakumarasivam A, Burtt G, Subkhankulova T, Arends MJ, et al: Differential expression of selected histone modifier genes in human solid cancers. BMC Genomics. 7:902006. View Article : Google Scholar

28 

Ahn MY, Kang DO, Na YJ, Yoon S, Choi WS, Kang KW, Chung HY, Jung JH, Min do S and Kim HS: Histone deacetylase inhibitor, apicidin, inhibits human ovarian cancer cell migration via class II histone deacetylase 4 silencing. Cancer Lett. 28(325): 189–199. 2012. View Article : Google Scholar

29 

Stronach EA, Alfraidi A, Rama N, Datler C, Studd JB, Agarwal R, Guney TG, Gourley C, Hennessy BT, Mills GB, et al: HDAC4-regulated STAT1 activation mediates platinum resistance in ovarian cancer. Cancer Res. 71:4412–4422. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Mottet D, Pirotte S, Lamour V, Hagedorn M, Javerzat S, Bikfalvi A, Bellahcène A, Verdin E and Castronovo V: HDAC4 represses p21(WAF1/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism. Oncogene. 28:243–256. 2009. View Article : Google Scholar

31 

Kang ZH, Wang CY, Zhang WL, Zhang JT, Yuan CH, Zhao PW, Lin YY, Hong S, Li CY and Wang L: Histone deacetylase HDAC4 promotes gastric cancer SGC-7901 cells progression via p21 repression. PLoS One. 9:e988942014. View Article : Google Scholar : PubMed/NCBI

32 

Fenner J, Stacer AC, Winterroth F, Johnson TD, Luker KE and Luker GD: Macroscopic stiffness of breast tumors predicts metastasis. Sci Rep. 4:55122014. View Article : Google Scholar : PubMed/NCBI

33 

Kaemmerer E, Melchels FP, Holzapfel BM, Meckel T, Hutmacher DW and Loessner D: Gelatine methacrylamide-based hydrogels: an alternative three-dimensional cancer cell culture system. Acta Biomater. 10:2551–2562. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Curry JM, Sprandio J, Cognetti D, Luginbuhl A, Bar-ad V, Pribitkin E and Tuluc M: Tumor microenvironment in head and neck squamous cell carcinoma. Semin Oncol. 41:217–234. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Cohen AL, Piccolo SR, Cheng L, Soldi R, Han B, Johnson WE and Bild AH: Genomic pathway analysis reveals that EZH2 and HDAC4 represent mutually exclusive epigenetic pathways across human cancers. BMC Med Genomics. 6:352013. View Article : Google Scholar : PubMed/NCBI

36 

Liu F, Pore N, Kim M, Voong KR, Dowling M, Maity A and Kao GD: Regulation of histone deacetylase 4 expression by the SP family of transcription factors. Mol Biol Cell. 17:585–597. 2006. View Article : Google Scholar :

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Copy and paste a formatted citation
Spandidos Publications style
Shen Y, Wei A, Kou Q, Zhu Q and Zhang L: Histone deacetylase 4 increases progressive epithelial ovarian cancer cells via repression of p21 on fibrillar collagen matrices. Oncol Rep 35: 948-954, 2016.
APA
Shen, Y., Wei, A., Kou, Q., Zhu, Q., & Zhang, L. (2016). Histone deacetylase 4 increases progressive epithelial ovarian cancer cells via repression of p21 on fibrillar collagen matrices. Oncology Reports, 35, 948-954. https://doi.org/10.3892/or.2015.4423
MLA
Shen, Y., Wei, A., Kou, Q., Zhu, Q., Zhang, L."Histone deacetylase 4 increases progressive epithelial ovarian cancer cells via repression of p21 on fibrillar collagen matrices". Oncology Reports 35.2 (2016): 948-954.
Chicago
Shen, Y., Wei, A., Kou, Q., Zhu, Q., Zhang, L."Histone deacetylase 4 increases progressive epithelial ovarian cancer cells via repression of p21 on fibrillar collagen matrices". Oncology Reports 35, no. 2 (2016): 948-954. https://doi.org/10.3892/or.2015.4423
Copy and paste a formatted citation
x
Spandidos Publications style
Shen Y, Wei A, Kou Q, Zhu Q and Zhang L: Histone deacetylase 4 increases progressive epithelial ovarian cancer cells via repression of p21 on fibrillar collagen matrices. Oncol Rep 35: 948-954, 2016.
APA
Shen, Y., Wei, A., Kou, Q., Zhu, Q., & Zhang, L. (2016). Histone deacetylase 4 increases progressive epithelial ovarian cancer cells via repression of p21 on fibrillar collagen matrices. Oncology Reports, 35, 948-954. https://doi.org/10.3892/or.2015.4423
MLA
Shen, Y., Wei, A., Kou, Q., Zhu, Q., Zhang, L."Histone deacetylase 4 increases progressive epithelial ovarian cancer cells via repression of p21 on fibrillar collagen matrices". Oncology Reports 35.2 (2016): 948-954.
Chicago
Shen, Y., Wei, A., Kou, Q., Zhu, Q., Zhang, L."Histone deacetylase 4 increases progressive epithelial ovarian cancer cells via repression of p21 on fibrillar collagen matrices". Oncology Reports 35, no. 2 (2016): 948-954. https://doi.org/10.3892/or.2015.4423
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