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Article

HDAC6 promotes cell proliferation and confers resistance to gefitinib in lung adenocarcinoma

  • Authors:
    • Zhihao Wang
    • Fang Tang
    • Pengchao Hu
    • Ying Wang
    • Jun Gong
    • Shaoxing Sun
    • Conghua Xie
  • View Affiliations / Copyright

    Affiliations: Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuchang, Wuhan 430071, P.R. China, Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuchang, Wuhan 430071, P.R. China
  • Pages: 589-597
    |
    Published online on: May 16, 2016
       https://doi.org/10.3892/or.2016.4811
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Abstract

Histone deacetylases (HDACs) are promising targets for cancer therapy, and first-generation HDAC inhibitors are currently in clinical trials for the treatment of cancer patients. HDAC6, which is a key regulator of many signaling pathways that are linked to cancer, has recently emerged as an attractive target for the treatment of cancer. In the present study, HDAC6 was found to be overexpressed in lung adenocarcinoma cell lines and was negatively correlated with the prognosis of patients with lung adenocarcinoma. Overexpression of HDAC6 promoted the proliferation of lung adenocarcinoma cells in a deacetylase activity-dependent manner. HDAC6 overexpression conferred resistance to gefitinib via the stabilization of epidermal growth factor receptor (EGFR). The inhibition of HDAC6 by CAY10603, a potent and selective inhibitor of HDAC6, inhibited the proliferation of lung adenocarcinoma cells and induced apoptosis. CAY10603 downregulated the levels of EGFR protein, which in turn inhibited activation of the EGFR signaling pathway. Moreover, CAY10603 synergized with gefitinib to induce apoptosis of the lung adenocarcinoma cell lines via the destabilization of EGFR. Taken together, our results suggest that the inhibition of HDAC6 may be a promising strategy for the treatment of lung adenocarcinoma.
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1 

Pao W and Girard N: New driver mutations in non-small-cell lung cancer. Lancet Oncol. 12:175–180. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Ettinger DS, Wood DE, Akerley W, Bazhenova LA, Borghaei H, Camidge DR, Cheney RT, Chirieac LR, D'Amico TA, Demmy TL, et al National comprehensive cancer network: Non-Small Cell Lung Cancer, Version 6.2015. J Natl Compr Canc Netw. 13:515–524. 2015.PubMed/NCBI

3 

Pao W and Chmielecki J: Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nat Rev Cancer. 10:760–774. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Popper HH, Ryska A, Tímár J and Olszewski W: Molecular testing in lung cancer in the era of precision medicine. Transl Lung Cancer Res. 3:291–300. 2014.

5 

Politi K and Herbst RS: Lung cancer in the era of precision medicine. Clin Cancer Res. 21:2213–2220. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Reck M, Heigener DF, Mok T, Soria JC and Rabe KF: Management of non-small-cell lung cancer: Recent developments. Lancet. 382:709–719. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Minucci S and Pelicci PG: Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer. 6:38–51. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Haberland M, Montgomery RL and Olson EN: The many roles of histone deacetylases in development and physiology: Implications for disease and therapy. Nat Rev Genet. 10:32–42. 2009. View Article : Google Scholar

9 

Falkenberg KJ and Johnstone RW: Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. Nat Rev Drug Discov. 13:673–691. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Duvic M, Olsen EA, Breneman D, Pacheco TR, Parker S, Vonderheid EC, Abuav R, Ricker JL, Rizvi S, Chen C, et al: Evaluation of the long-term tolerability and clinical benefit of vorinostat in patients with advanced cutaneous T-cell lymphoma. Clin Lymphoma Myeloma. 9:412–416. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Marks PA and Breslow R: Dimethyl sulfoxide to vorinostat: Development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol. 25:84–90. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Bruserud Ø, Stapnes C, Ersvaer E, Gjertsen BT and Ryningen A: Histone deacetylase inhibitors in cancer treatment: A review of the clinical toxicity and the modulation of gene expression in cancer cell. Curr Pharm Biotechnol. 8:388–400. 2007. View Article : Google Scholar

13 

Marsoni S, Damia G and Camboni G: A work in progress: The clinical development of histone deacetylase inhibitors. Epigenetics. 3:164–171. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Kaliszczak M, Trousil S, Åberg O, Perumal M, Nguyen QD and Aboagye EO: A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth. Br J Cancer. 108:342–350. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Namdar M, Perez G, Ngo L and Marks PA: Selective inhibition of histone deacetylase 6 (HDAC6) induces DNA damage and sensitizes transformed cells to anticancer agents. Proc Natl Acad Sci USA. 107:20003–20008. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Krämer OH, Mahboobi S and Sellmer A: Drugging the HDAC6-HSP90 interplay in malignanT cells. Trends Pharmacol Sci. 35:501–509. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Zhang Y, Li N, Caron C, Matthias G, Hess D, Khochbin S and Matthias P: HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo. EMBO J. 22:1168–1179. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Park SJ, Kim JK, Bae HJ, Eun JW, Shen Q, Kim HS, Shin WC, Yang HD, Lee EK, You JS, et al: HDAC6 sustains growth stimulation by prolonging the activation of EGF receptor through the inhibition of rabaptin-5-mediated early endosome fusion in gastric cancer. Cancer Lett. 354:97–106. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Aldana-Masangkay GI and Sakamoto KM: The role of HDAC6 in cancer. J Biomed Biotechnol. 2011:8758242011. View Article : Google Scholar

20 

Kozikowski AP, Tapadar S, Luchini DN, Kim KH and Billadeau DD: Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: A new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6. J Med Chem. 51:4370–4373. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Yang Y, Ran J, Liu M, Li D, Li Y, Shi X, Meng D, Pan J, Ou G, Aneja R, et al: CYLD mediates ciliogenesis in multiple organs by deubiquitinating Cep70 and inactivating HDAC6. Cell Res. 24:1342–1353. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Ran J, Yang Y, Li D, Liu M and Zhou J: Deacetylation of α-tubulin and cortactin is required for HDAC6 to trigger ciliary disassembly. Sci Rep. 5:129172015. View Article : Google Scholar

23 

Győrffy B, Surowiak P, Budczies J and Lánczky A: Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS One. 8:e822412013. View Article : Google Scholar

24 

Yu HA, Arcila ME, Rekhtman N, Sima CS, Zakowski MF, Pao W, Kris MG, Miller VA, Ladanyi M and Riely GJ: Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res. 19:2240–2247. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Deribe YL, Wild P, Chandrashaker A, Curak J, Schmidt MH, Kalaidzidis Y, Milutinovic N, Kratchmarova I, Buerkle L, Fetchko MJ, et al: Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6. Sci Signal. 2:ra842009.PubMed/NCBI

26 

Gao YS, Hubbert CC and Yao TP: The microtubule-associated histone deacetylase 6 (HDAC6) regulates epidermal growth factor receptor (EGFR) endocytic trafficking and degradation. J Biol Chem. 285:11219–11226. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Gradilone SA, Radtke BN, Bogert PS, Huang BQ, Gajdos GB and LaRusso NF: HDAC6 inhibition restores ciliary expression and decreases tumor growth. Cancer Res. 73:2259–2270. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Dhanyamraju PK, Holz PS, Finkernagel F, Fendrich V and Lauth M: Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway. Mol Cancer Ther. 14:727–739. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Ai J, Wang Y, Dar JA, Liu J, Liu L, Nelson JB and Wang Z: HDAC6 regulates androgen receptor hypersensitivity and nuclear localization via modulating Hsp90 acetylation in castration-resistant prostate cancer. Mol Endocrinol. 23:1963–1972. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Haggarty SJ, Koeller KM, Wong JC, Grozinger CM and Schreiber SL: Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci USA. 100:4389–4394. 2003. View Article : Google Scholar : PubMed/NCBI

31 

Kaluza D, Kroll J, Gesierich S, Yao TP, Boon RA, Hergenreider E, Tjwa M, Rössig L, Seto E, Augustin HG, et al: Class IIb HDAC6 regulates endothelial cell migration and angiogenesis by deacety-lation of cortactin. EMBO J. 30:4142–4156. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Weihua Z, Tsan R, Huang WC, Wu Q, Chiu CH, Fidler IJ and Hung MC: Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer Cell. 13:385–393. 2008. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang Z, Tang F, Hu P, Wang Y, Gong J, Sun S and Xie C: HDAC6 promotes cell proliferation and confers resistance to gefitinib in lung adenocarcinoma. Oncol Rep 36: 589-597, 2016.
APA
Wang, Z., Tang, F., Hu, P., Wang, Y., Gong, J., Sun, S., & Xie, C. (2016). HDAC6 promotes cell proliferation and confers resistance to gefitinib in lung adenocarcinoma. Oncology Reports, 36, 589-597. https://doi.org/10.3892/or.2016.4811
MLA
Wang, Z., Tang, F., Hu, P., Wang, Y., Gong, J., Sun, S., Xie, C."HDAC6 promotes cell proliferation and confers resistance to gefitinib in lung adenocarcinoma". Oncology Reports 36.1 (2016): 589-597.
Chicago
Wang, Z., Tang, F., Hu, P., Wang, Y., Gong, J., Sun, S., Xie, C."HDAC6 promotes cell proliferation and confers resistance to gefitinib in lung adenocarcinoma". Oncology Reports 36, no. 1 (2016): 589-597. https://doi.org/10.3892/or.2016.4811
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Z, Tang F, Hu P, Wang Y, Gong J, Sun S and Xie C: HDAC6 promotes cell proliferation and confers resistance to gefitinib in lung adenocarcinoma. Oncol Rep 36: 589-597, 2016.
APA
Wang, Z., Tang, F., Hu, P., Wang, Y., Gong, J., Sun, S., & Xie, C. (2016). HDAC6 promotes cell proliferation and confers resistance to gefitinib in lung adenocarcinoma. Oncology Reports, 36, 589-597. https://doi.org/10.3892/or.2016.4811
MLA
Wang, Z., Tang, F., Hu, P., Wang, Y., Gong, J., Sun, S., Xie, C."HDAC6 promotes cell proliferation and confers resistance to gefitinib in lung adenocarcinoma". Oncology Reports 36.1 (2016): 589-597.
Chicago
Wang, Z., Tang, F., Hu, P., Wang, Y., Gong, J., Sun, S., Xie, C."HDAC6 promotes cell proliferation and confers resistance to gefitinib in lung adenocarcinoma". Oncology Reports 36, no. 1 (2016): 589-597. https://doi.org/10.3892/or.2016.4811
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