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Tid1 functions as a tumour suppressor in head and neck squamous cell carcinoma

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Author(s): Chen, CY (Chen, Chi-Yuan); Chiou, SH (Chiou, Shih-Hwa); Huang, CY (Huang, Chih-Yang); Jan, CI (Jan, Chia-Ing); Lin, SC (Lin, Shu-Chun); Hu, WY (Hu, Wen-Yuan); Chou, SH (Chou, Shiu-Huey); Liu, CJ (Liu, Chung-Ji); Lo, JF (Lo, Jeng-Fan)

Title: Tid1 functions as a tumour suppressor in head and neck squamous cell carcinoma Source: JOURNAL OF PATHOLOGY, 219 (3): 347-355 NOV 2009

Language: English Document Type: Article

Author Keywords: Tid1; head and neck cancer; EGFR; AKT; tumour suppressor

KeyWords Plus: SIGNALING NETWORK; HUMAN HOMOLOG; CANCER; DROSOPHILA;

HTID-1; CARCINOGENESIS; ACTIVATION; CHAPERONES; EXPRESSION; APOPTOSIS Abstract: Human tumourous imaginal disc (Tid1), a human homologue of the Drosophila tumour suppressor protein Tid56, is involved in multiple intracellular signalling pathways such as apoptosis, cell proliferation, and cell survival. Here, we investigated the anti-tumourigenic activity of Tid1 in head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo.

Firstly, the clinical association between Tid1 expression and progression of HNSCC was explored. It was found that expression of Tid1 was negatively associated with tumour status, recurrence, and survival prognosis using immunohistochemical analysis of primary HNSCC patient tumour tissue. Secondly, ectopic expression of Tid1 in HNSCC cells was shown to significantly inhibit cell proliferation, migration, invasion, anchorage-independent growth, and xenotransplantation tumourigenicity. Thirdly, we showed that overexpression of Tid1

attenuated EGFR activity and blocked the activation of AKT in HNSCC cells, which are known to be involved in the regulation of survival in HNSCC cells. On the other hand, ectopic

expression of constitutively active AKT greatly reduced apoptosis induced by Tid1

overexpression. Together, these findings suggest that Tid1 functions as a tumour suppressor in HNSCC tumourigenesis. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Addresses: [Chen, Chi-Yuan; Chiou, Shih-Hwa; Lin, Shu-Chun; Lo, Jeng-Fan] Natl Yang Ming Univ, Inst Oral Biol, Taipei 11217, Taiwan; [Chiou, Shih-Hwa] Taichung Vet Gen Hosp, Dept Med Res & Educ, Taipei, Taiwan; [Huang, Chih-Yang] China Med Univ, Inst Med Sci, Taichung, Taiwan; [Huang, Chih-Yang] China Med Univ, Grad Inst Chinese Med Sci, Taichung, Taiwan; [Huang, Chih-Yang] China Med Univ, Inst Basic Med Sci, Taichung, Taiwan; [Huang, Chih-Yang] Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung, Taiwan; [Jan, Chia-Ing] China Med Univ & Hosp, Dept Pathol, Taichung, Taiwan; [Hu, Wen-Yuan] Biosettia Inc, San Diego, CA USA; [Chou, Shiu-Huey] Fu Jen Catholic Univ, Dept Life Sci, Taipei, Taiwan; [Liu, Chung-Ji] Mackay Mem Hosp, Dept Oral & Maxillofacial Surg, Taipei, Taiwan Reprint Address: Lo, JF, Natl Yang Ming Univ, Inst Oral Biol, 155,Sect 2,Li Nung St, Taipei 11217, Taiwan.

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E-mail Address: [email protected] Funding Acknowledgement:

Funding Agency Grant Number

National Science Council

NSC95N444 NSC97N456

NSC973111B075001MY3

Taipei Veterans General Hospital

V95E2007 V95132013 V96ER2016 V97ER2018 V98ER2018

National Yang-Ming University (Ministry of Education, Aim for the Top University Plan)

96ADD122 97ACD113 97ACT302 98ACT302

We thank Dr KW Chang (Institute of Oral Biology, National Yang-Ming University) for providing critical comments. This study was supported by research grants from the National Science Council (NSC95N444, NSC97N456 and NSC973111B075001MY3). Taipei Veterans General Hospital (V95E2007, V95132013, V96ER2016, V97ER2018, and V98ER2018), and National Yang-Ming University (Ministry of Education, Aim for the Top University Plan) (96ADD122, 97ACD113, 97ACT302, and 98ACT302) in Taiwan, ROC.

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Publisher: JOHN WILEY & SONS LTD

Publisher Address: THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND

ISSN: 0022-3417 DOI: 10.1002/path.2604

29-char Source Abbrev.: J PATHOL ISO Source Abbrev.: J. Pathol.

Source Item Page Count: 9

Subject Category: Oncology; Pathology ISI Document Delivery No.: 513SI

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