Top

Clinical Oral Investigations

Published in:

Open Access 01-04-2016 | Original Article

Daxx and TCF4 interaction links to oral squamous cell carcinoma growth by promoting cell cycle progression via induction of cyclin D1 expression

Authors: Gu-Jiun Lin, Yen-Sung Huang, Chih-Kung Lin, Shing-Hwa Huang, Hsiu-Ming Shih, Huey-Kang Sytwu, Yuan-Wu Chen

Published in: Clinical Oral Investigations | Issue 3/2016

Abstract

Objectives

Death domain-associated protein (Daxx) has been recently implicated as a positive factor in ovarian cancer and prostate cancer, but the role of Daxx in oral squamous cell carcinoma (OSCC) has never been addressed. Herein, we investigate the expression and function of Daxx in OSCC.

Materials and methods

RT-quantitative PCR, Western blotting, and immunohistochemistry were used to evaluation of the expression of Daxx in human OSCC cell lines and clinical surgical specimens. Short hairpin RNA targeting Daxx was transduced by lentivirus infection to knockdown the expression of Daxx in SAS and SCC25 cell lines, and the influence of this knockdown was evaluated by analyzing the growth and the cell cycle in transduced cells. Immunoprecipitation and sequential chromatin immunoprecipitation-quantitative PCR were used to analyze the associations between Daxx, TCF4, and cyclin D1 promoter. Xenograft tumor model was used to evaluate the in vivo tumorigenicity of Daxx in OSCC.

Results

Daxx mRNA and protein expression are elevated in several OSCC cell lines and human OSCC samples in comparison to those in normal tissue. We further find that depletion of Daxx decreases OSCC cell growth activity through G1 cell cycle arrest. Daxx silencing reduces cyclin D1 expression via a Daxx-TCF4 interaction, whereas the Daxx depletion-mediated G1 arrest can be relieved by ectopic expression of cyclin D1. Moreover, we show that in OSCC clinical samples, the expression of Daxx is significantly correlated with that of cyclin D1.

Conclusion

Our data demonstrate the importance of Daxx in regulation of cyclin D1 expression and provide the first evidence that Daxx exhibits tumor-promoting activity in OSCC.

Clinical relevance

Daxx plays an important role in malignant transformation of OSCC and may serves as a target for cancer prevention and treatment.

Siegel R, Desantis C, Jemal A (2014) Colorectal cancer statistics, 2014. CA Cancer J Clin 64:104–117CrossRefPubMed

Liu SY, Lu CL, Chiou CT, Yen CY, Liaw GA, Chen YC, Liu YC, Chiang WF (2010) Surgical outcomes and prognostic factors of oral cancer associated with betel quid chewing and tobacco smoking in Taiwan. Oral Oncol 46:276–282CrossRefPubMed

Salomoni P, Khelifi AF (2006) Daxx: death or survival protein? Trends Cell Biol 16:97–104CrossRefPubMed

Shih HM, Chang CC, Kuo HY, Lin DY (2007) Daxx mediates SUMO-dependent transcriptional control and subnuclear compartmentalization. Biochem Soc Trans 35:1397–1400CrossRefPubMed

Huang YS, Chang CC, Huang TC, Hsieh YL, Shih HM (2012) Daxx interacts with and modulates the activity of CREB. Cell Cycle 11:99–108CrossRefPubMed

Goldberg AD, Banaszynski LA, Noh KM, Lewis PW, Elsaesser SJ, Stadler S, Dewell S, Law M, Guo X, Li X, Wen D, Chapgier A, DeKelver RC, Miller JC, Lee YL, Boydston EA, Holmes MC, Gregory PD, Greally JM, Rafii S, Yang C, Scambler PJ, Garrick D, Gibbons RJ, Higgs DR, Cristea IM, Urnov FD, Zheng D, Allis CD (2010) Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell 140:678–691CrossRefPubMedPubMedCentral

Jiao Y, Shi C, Edil BH, de Wilde RF, Klimstra DS, Maitra A, Schulick RD, Tang LH, Wolfgang CL, Choti MA, Velculescu VE, Diaz LA Jr, Vogelstein B, Kinzler KW, Hruban RH, Papadopoulos N (2011) DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 331:1199–1203CrossRefPubMedPubMedCentral

Tsourlakis MC, Schoop M, Plass C, Huland H, Graefen M, Steuber T, Schlomm T, Simon R, Sauter G, Sirma H, Minner S (2013) Overexpression of the chromatin remodeler death-domain-associated protein in prostate cancer is an independent predictor of early prostate-specific antigen recurrence. Hum Pathol 44:1789–1796CrossRefPubMed

Pan WW, Zhou JJ, Liu XM, Xu Y, Guo LJ, Yu C, Shi QH, Fan HY (2013) Death domain-associated protein DAXX promotes ovarian cancer development and chemoresistance. J Biol Chem 288:13620–13630CrossRefPubMedPubMedCentral

10.

Tang J, Qu LK, Zhang J, Wang W, Michaelson JS, Degenhardt YY, El-Deiry WS, Yang X (2006) Critical role for Daxx in regulating Mdm2. Nat Cell Biol 8:855–862CrossRefPubMed

11.

Song MS, Salmena L, Carracedo A, Egia A, Lo-Coco F, Teruya-Feldstein J, Pandolfi PP (2008) The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature 455:813–817CrossRefPubMedPubMedCentral

12.

Chen YW, Lin GJ, Chia WT, Lin CK, Chuang YP, Sytwu HK (2009) Triptolide exerts anti-tumor effect on oral cancer and KB cells in vitro and in vivo. Oral Oncol 45:562–568CrossRefPubMed

13.

Wu MJ, Jan CI, Tsay YG, Yu YH, Huang CY, Lin SC, Liu CJ, Chen YS, Lo JF, Yu CC (2010) Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling. Mol Cancer 9:283–298CrossRefPubMedPubMedCentral

14.

Michaelson JS, Leder P (2003) RNAi reveals anti-apoptotic and transcriptionally repressive activities of DAXX. J Cell Sci 116:345–352CrossRefPubMed

15.

Nateri AS, Spencer-Dene B, Behrens A (2005) Interaction of phosphorylated c-Jun with TCF4 regulates intestinal cancer development. Nature 437:281–285CrossRefPubMed

16.

Chang CC, Naik MT, Huang YS, Jeng JC, Liao PH, Kuo HY, Ho CC, Hsieh YL, Lin CH, Huang NJ, Naik NM, Kung CC, Lin SY, Chen RH, Chang KS, Huang TH, Shih HM (2011) Structural and functional roles of Daxx SIM phosphorylation in SUMO paralog-selective binding and apoptosis modulation. Mol Cell 42:62–74CrossRefPubMed

17.

Huang YS, Shih HM (2009) Daxx positively modulates beta-catenin/TCF4-mediated transcriptional potential. Biochem Biophys Res Commun 386:762–768CrossRefPubMed

18.

Hanken H, Grobe A, Cachovan G, Smeets R, Simon R, Sauter G, Heiland M, Blessmann M (2014) CCND1 amplification and cyclin D1 immunohistochemical expression in head and neck squamous cell carcinomas. Clin Oral Investig 18:269–276CrossRefPubMed

19.

Tetsu O, McCormick F (1999) Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398:422–426CrossRefPubMed

20.

Zhao Y, Yu D, Li H, Nie P, Zhu Y, Liu S, Zhu M, Fang B (2014) Cyclin D1 overexpression is associated with poor clinicopathological outcome and survival in oral squamous cell carcinoma in Asian populations: insights from a meta-analysis. PLoS One 9:e93210–e93218CrossRefPubMedPubMedCentral

21.

Kwan PS, Lau CC, Chiu YT, Man C, Liu J, Tang KD, Wong YC, Ling MT (2013) Daxx regulates mitotic progression and prostate cancer predisposition. Carcinogenesis 34:750–759CrossRefPubMed

22.

Pan WW, Yi FP, Cao LX, Liu XM, Shen ZF, Bu YQ, Xu Y, Fan HY, Song FZ (2013) DAXX silencing suppresses mouse ovarian surface epithelial cell growth by inducing senescence and DNA damage. Gene 526:287–294CrossRefPubMed

23.

da Silva SD, Ferlito A, Takes RP, Brakenhoff RH, Valentin MD, Woolgar JA, Bradford CR, Rodrigo JP, Rinaldo A, Hier MP, Kowalski LP (2011) Advances and applications of oral cancer basic research. Oral Oncol 47:783–791CrossRefPubMed

24.

Emelyanov AV, Kovac CR, Sepulveda MA, Birshtein BK (2002) The interaction of Pax5 (BSAP) with Daxx can result in transcriptional activation in B cells. J Biol Chem 277:11156–11164CrossRefPubMed

25.

Salomoni P (2013) The PML-interacting protein DAXX: histone loading gets into the picture. Front Oncol 3:152–162CrossRefPubMedPubMedCentral

Title: Daxx and TCF4 interaction links to oral squamous cell carcinoma growth by promoting cell cycle progression via induction of cyclin D1 expression
Authors: Gu-Jiun Lin
Yen-Sung Huang
Chih-Kung Lin
Shing-Hwa Huang
Hsiu-Ming Shih
Huey-Kang Sytwu
Yuan-Wu Chen
Publication date: 01-04-2016
Publisher: Springer Berlin Heidelberg
Published in: Clinical Oral Investigations / Issue 3/2016
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-015-1536-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Daxx and TCF4 interaction links to oral squamous cell carcinoma growth by promoting cell cycle progression via induction of cyclin D1 expression

Abstract

Objectives

Materials and methods

Results

Conclusion

Clinical relevance

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Materials and methods

Results

Conclusion

Clinical relevance

Please log in to get access to this content

Other articles of this Issue 3/2016

Relationship between toothpastes properties and patient-reported discomfort: crossover study

Immediate tooth replantation in rats: effect of systemic antibiotic therapy with amoxicillin and tetracycline

The effectiveness of dentifrices without and with sodium lauryl sulfate on plaque, gingivitis and gingival abrasion—a randomized clinical trial

A temporary filling material during endodontic treatment may cause tooth fractures in two-surface class II cavities in vitro

Influence of mechanical compression on human periodontal ligament fibroblasts and osteoblasts

IL-17A and IL-17F polymorphisms in rheumatoid arthritis and Sjögren’s syndrome