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Article

The Hippo pathway transcriptional co-activator, YAP, confers resistance to cisplatin in human oral squamous cell carcinoma

  • Authors:
    • Kyohei Yoshikawa
    • Kazuma Noguchi
    • Yoshiro Nakano
    • Michiyo Yamamura
    • Kazuki Takaoka
    • Tomoko Hashimoto-Tamaoki
    • Hiromitsu Kishimoto
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan, Department of Genetics, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
  • Pages: 2364-2370
    |
    Published online on: April 1, 2015
       https://doi.org/10.3892/ijo.2015.2948
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Abstract

Cisplatin (CDDP) is widely used to treat oral squamous cell carcinoma (OSCC), however, many patients exhibit acquired drug resistance. Yes-associated protein (YAP) is a transcriptional co-activator of the Hippo pathway that regulates organ size and promotes cell proliferation. YAP overexpression correlates with epithelial-mesenchymal transition and nodal metastasis, resulting in anti-tubulin drug resistance. Whether YAP overexpression is the cause of CDDP resistance in cancer cells is unclear, therefore, we investigated the correlation between YAP expression and CDDP sensitivity. We established three CDDP-resistant cell lines (OSC-19-R, SCCKN-R and HSC-3-R) from the OSCC parental cell lines. We also examined the expression levels of ATP7B, GST-π and ERCC1, which are strongly associated with CDDP resistance, and Hippo pathway-related proteins by western blotting. Using immunocytochemistry, we examined the cellular localization of YAP. Additionally, following knockdown of YAP using short interfering RNAs (siRNAs), we analyzed changes in sensitivity to CDDP. Compared with parental OSC-19 cells, OSC-19-R cells were obviously larger. Expression levels of YAP were not significantly different between OSC-19 and OSC-19-R. However, expression levels of phosphorylated YAP in OSC-19-R were decreased. We observed translocation of YAP from the cytoplasm to the nucleus in OSC-19-R cells. Knockdown of YAP using siRNAs revealed that sensitivity to CDDP was significantly increased. Translocation of YAP correlated with the acquisition of CDDP resistance. YAP could be a new therapeutic target for the treatment of patients with cancer that are resistant to CDDP.
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1 

Haddad RI and Shin DM: Recent advances in head and neck cancer. N Engl J Med. 359:1143–1154. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Overgaard J, Mohanti BK, Begum N, Ali R, Agarwal JP, Kuddu M, Bhasker S, Tatsuzaki H and Grau C: Five versus six fractions of radiotherapy per week for squamous-cell carcinoma of the head and neck (IAEA-ACC study): A randomised, multi-centre trial. Lancet Oncol. 11:553–560. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Roepman P, Wessels LF, Kettelarij N, Kemmeren P, Miles AJ, Lijnzaad P, Tilanus MG, Koole R, Hordijk GJ, van der Vliet PC, et al: An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas. Nat Genet. 37:182–186. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Weaver A, Fleming S, Ensley J, Kish JA, Jacobs J, Kinzie J, Crissman J and Al-Sarraf M: Superior clinical response and survival rates with initial bolus of cisplatin and 120 hour infusion of 5-fluorouracil before definitive therapy for locally advanced head and neck cancer. Am J Surg. 148:525–529. 1984. View Article : Google Scholar : PubMed/NCBI

5 

Rooney M, Kish J, Jacobs J, Kinzie J, Weaver A, Crissman J and Al-Sarraf M: Improved complete response rate and survival in advanced head and neck cancer after three-course induction therapy with 120-hour 5-FU infusion and cisplatin. Cancer. 55:1123–1128. 1985. View Article : Google Scholar : PubMed/NCBI

6 

Wang D and Lippard SJ: Cellular processing of platinum anti-cancer drugs. Nat Rev Drug Discov. 4:307–320. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Hall MD, Okabe M, Shen DW, Liang XJ and Gottesman MM: The role of cellular accumulation in determining sensitivity to platinum-based chemotherapy. Annu Rev Pharmacol Toxicol. 48:495–535. 2008. View Article : Google Scholar

8 

Shen DW, Pouliot LM, Hall MD and Gottesman MM: Cisplatin resistance: A cellular self-defense mechanism resulting from multiple epigenetic and genetic changes. Pharmacol Rev. 64:706–721. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Avruch J, Zhou D, Fitamant J and Bardeesy N: Mst1/2 signalling to Yap: Gatekeeper for liver size and tumour development. Br J Cancer. 104:24–32. 2011. View Article : Google Scholar :

10 

Wang K, Degerny C, Xu M and Yang XJ: YAP, TAZ, and Yorkie: A conserved family of signal-responsive transcriptional coregulators in animal development and human disease. Biochem Cell Biol. 87:77–91. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Yuan M, Tomlinson V, Lara R, Holliday D, Chelala C, Harada T, Gangeswaran R, Manson-Bishop C, Smith P, Danovi SA, et al: Yes-associated protein (YAP) functions as a tumor suppressor in breast. Cell Death Differ. 15:1752–1759. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Vidal M and Cagan RL: Drosophila models for cancer research. Curr Opin Genet Dev. 16:10–16. 2006. View Article : Google Scholar

13 

Nylander K, Coates PJ and Hall PA: Characterization of the expression pattern of p63 alpha and delta Np63 alpha in benign and malignant oral epithelial lesions. Int J Cancer. 87:368–372. 2000. View Article : Google Scholar : PubMed/NCBI

14 

Lo Muzio L, Santarelli A, Caltabiano R, Rubini C, Pieramici T, Trevisiol L, Carinci F, Leonardi R, De Lillo A, Lanzafame S, et al: p63 overexpression associates with poor prognosis in head and neck squamous cell carcinoma. Hum Pathol. 36:187–194. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Ge L, Smail M, Meng W, Shyr Y, Ye F, Fan KH, Li X, Zhou HM and Bhowmick NA: Yes-associated protein expression in head and neck squamous cell carcinoma nodal metastasis. PLoS One. 6:e275292011. View Article : Google Scholar : PubMed/NCBI

16 

Zhao Y, Khanal P, Savage P, She YM, Cyr TD and Yang X: YAP-induced resistance of cancer cells to antitubulin drugs is modulated by a Hippo-independent pathway. Cancer Res. 74:4493–4503. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Yamamura M, Noguchi K, Nakano Y, Segawa E, Zushi Y, Takaoka K, Kishimoto H, Hashimoto-Tamaoki T and Urade M: Functional analysis of Zyxin in cell migration and invasive potential of oral squamous cell carcinoma cells. Int J Oncol. 42:873–880. 2013.PubMed/NCBI

18 

Köberle B, Tomicic MT, Usanova S and Kaina B: Cisplatin resistance: Preclinical findings and clinical implications. Biochim Biophys Acta. 1806:172–182. 2010.PubMed/NCBI

19 

Liu AM, Wong KF, Jiang X, Qiao Y and Luk JM: Regulators of mammalian Hippo pathway in cancer. Biochim Biophys Acta. 1826:357–364. 2012.PubMed/NCBI

20 

Solioz M and Vulpe C: CPx-type ATPases: A class of P-type ATPases that pump heavy metals. Trends Biochem Sci. 21:237–241. 1996. View Article : Google Scholar : PubMed/NCBI

21 

Culotta VC, Lin SJ, Schmidt P, Klomp LW, Casareno RL and Gitlin J: Intracellular pathways of copper trafficking in yeast and humans. Adv Exp Med Biol. 448:247–254. 1999.PubMed/NCBI

22 

Katano K, Safaei R, Samimi G, Holzer A, Rochdi M and Howell SB: The copper export pump ATP7B modulates the cellular pharmacology of carboplatin in ovarian carcinoma cells. Mol Pharmacol. 64:466–473. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Samimi G, Katano K, Holzer AK, Safaei R and Howell SB: Modulation of the cellular pharmacology of cisplatin and its analogs by the copper exporters ATP7A and ATP7B. Mol Pharmacol. 66:25–32. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Safaei R and Howell SB: Copper transporters regulate the cellular pharmacology and sensitivity to Pt drugs. Crit Rev Oncol Hematol. 53:13–23. 2005. View Article : Google Scholar

25 

Yoshizawa K, Nozaki S, Kitahara H, Ohara T, Kato K, Kawashiri S and Yamamoto E: Copper efflux transporter (ATP7B) contributes to the acquisition of cisplatin-resistance in human oral squamous cell lines. Oncol Rep. 18:987–991. 2007.PubMed/NCBI

26 

Hong W and Guan KL: The YAP and TAZ transcription co-activators: Key downstream effectors of the mammalian Hippo pathway. Semin Cell Dev Biol. 23:785–793. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Sudol M and Harvey KF: Modularity in the Hippo signaling pathway. Trends Biochem Sci. 35:627–633. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Yu FX and Guan KL: The Hippo pathway: Regulators and regulations. Genes Dev. 27:355–371. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Guo X and Zhao B: Integration of mechanical and chemical signals by YAP and TAZ transcription coactivators. Cell Biosci. 3:332013. View Article : Google Scholar : PubMed/NCBI

30 

Lai D, Visser-Grieve S and Yang X: Tumour suppressor genes in chemotherapeutic drug response. Biosci Rep. 32:361–374. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Carey TE, Van Dyke DL and Worsham MJ: Nonrandom chromosome aberrations and clonal populations in head and neck cancer. Anticancer Res. 13(6B): 2561–2567. 1993.PubMed/NCBI

32 

Snijders AM, Schmidt BL, Fridlyand J, Dekker N, Pinkel D, Jordan RC and Albertson DG: Rare amplicons implicate frequent deregulation of cell fate specification pathways in oral squamous cell carcinoma. Oncogene. 24:4232–4242. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Lai D, Ho KC, Hao Y and Yang X: Taxol resistance in breast cancer cells is mediated by the hippo pathway component TAZ and its downstream transcriptional targets Cyr61 and CTGF. Cancer Res. 71:2728–2738. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Visser S and Yang X: Identification of LATS transcriptional targets in HeLa cells using whole human genome oligonucleotide microarray. Gene. 449:22–29. 2010. View Article : Google Scholar

35 

Kawahara M, Hori T, Chonabayashi K, Oka T, Sudol M and Uchiyama T: Kpm/Lats2 is linked to chemosensitivity of leukemic cells through the stabilization of p73. Blood. 112:3856–3866. 2008. View Article : Google Scholar : PubMed/NCBI

36 

Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C, Inui M, Montagner M, Parenti AR, Poletti A, et al: The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells. Cell. 147:759–772. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Frisch SM, Schaller M and Cieply B: Mechanisms that link the oncogenic epithelial-mesenchymal transition to suppression of anoikis. J Cell Sci. 126:21–29. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yoshikawa K, Noguchi K, Nakano Y, Yamamura M, Takaoka K, Hashimoto-Tamaoki T and Kishimoto H: The Hippo pathway transcriptional co-activator, YAP, confers resistance to cisplatin in human oral squamous cell carcinoma. Int J Oncol 46: 2364-2370, 2015.
APA
Yoshikawa, K., Noguchi, K., Nakano, Y., Yamamura, M., Takaoka, K., Hashimoto-Tamaoki, T., & Kishimoto, H. (2015). The Hippo pathway transcriptional co-activator, YAP, confers resistance to cisplatin in human oral squamous cell carcinoma. International Journal of Oncology, 46, 2364-2370. https://doi.org/10.3892/ijo.2015.2948
MLA
Yoshikawa, K., Noguchi, K., Nakano, Y., Yamamura, M., Takaoka, K., Hashimoto-Tamaoki, T., Kishimoto, H."The Hippo pathway transcriptional co-activator, YAP, confers resistance to cisplatin in human oral squamous cell carcinoma". International Journal of Oncology 46.6 (2015): 2364-2370.
Chicago
Yoshikawa, K., Noguchi, K., Nakano, Y., Yamamura, M., Takaoka, K., Hashimoto-Tamaoki, T., Kishimoto, H."The Hippo pathway transcriptional co-activator, YAP, confers resistance to cisplatin in human oral squamous cell carcinoma". International Journal of Oncology 46, no. 6 (2015): 2364-2370. https://doi.org/10.3892/ijo.2015.2948
Copy and paste a formatted citation
x
Spandidos Publications style
Yoshikawa K, Noguchi K, Nakano Y, Yamamura M, Takaoka K, Hashimoto-Tamaoki T and Kishimoto H: The Hippo pathway transcriptional co-activator, YAP, confers resistance to cisplatin in human oral squamous cell carcinoma. Int J Oncol 46: 2364-2370, 2015.
APA
Yoshikawa, K., Noguchi, K., Nakano, Y., Yamamura, M., Takaoka, K., Hashimoto-Tamaoki, T., & Kishimoto, H. (2015). The Hippo pathway transcriptional co-activator, YAP, confers resistance to cisplatin in human oral squamous cell carcinoma. International Journal of Oncology, 46, 2364-2370. https://doi.org/10.3892/ijo.2015.2948
MLA
Yoshikawa, K., Noguchi, K., Nakano, Y., Yamamura, M., Takaoka, K., Hashimoto-Tamaoki, T., Kishimoto, H."The Hippo pathway transcriptional co-activator, YAP, confers resistance to cisplatin in human oral squamous cell carcinoma". International Journal of Oncology 46.6 (2015): 2364-2370.
Chicago
Yoshikawa, K., Noguchi, K., Nakano, Y., Yamamura, M., Takaoka, K., Hashimoto-Tamaoki, T., Kishimoto, H."The Hippo pathway transcriptional co-activator, YAP, confers resistance to cisplatin in human oral squamous cell carcinoma". International Journal of Oncology 46, no. 6 (2015): 2364-2370. https://doi.org/10.3892/ijo.2015.2948
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