The Hippo transducer TAZ promotes epithelial to mesenchymal transition and cancer stem cell maintenance in oral cancer.

Autor: Li Z; Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Jiangsu 210029, China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu 210029, China., Wang Y; Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Jiangsu 210029, China., Zhu Y; Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Jiangsu 210029, China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu 210029, China., Yuan C; Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Jiangsu 210029, China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu 210029, China., Wang D; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu 210029, China., Zhang W; Department of Oral Pathology, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu 210029, China., Qi B; Department of Oral Pathology, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu 210029, China., Qiu J; Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Jiangsu 210029, China., Song X; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu 210029, China., Ye J; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu 210029, China., Wu H; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu 210029, China., Jiang H; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu 210029, China., Liu L; Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Jiangsu 210029, China; Department of Oral Pathology, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu 210029, China., Zhang Y; Department of Head & Neck Oncology, Jiangsu Cancer Hospital, Jiangsu 210000, China., Song LN; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, NY 10032, USA., Yang J; Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Jiangsu 210029, China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu 210029, China. Electronic address: cj992118@yahoo.com., Cheng J; Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Jiangsu 210029, China; Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Jiangsu 210029, China. Electronic address: leonardo_cheng@163.com.
Jazyk: angličtina
Zdroj: Molecular oncology [Mol Oncol] 2015 Jun; Vol. 9 (6), pp. 1091-105. Date of Electronic Publication: 2015 Feb 09.
DOI: 10.1016/j.molonc.2015.01.007
Abstrakt: The Hippo pathway has emerged as a fundamental regulator in tissue growth, organ size and stem cell functions, and tumorigenesis when deregulated. However, its roles and associated molecular mechanisms underlying oral squamous cell carcinoma (OSCC) initiation and progression remain largely unknown. Here, we identified TAZ, the downstream effector of Hippo signaling, as a novel bona fide oncogene by promoting cell proliferation, migration/invasion and chemoresistance in OSCC. TAZ promoted epithelial-to-mesenchymal transition (EMT) and also was involved in TGF-β1-induced EMT in oral cancer cells. Furthermore, enriched TAZ sustained self-renewal, maintenance, tumor-seeding potential of oral cancer stem cells (CSCs). Remarkably, enforced TAZ overexpression conferred CSCs-like properties on differentiated non-CSCs and fueled phenotypic transition from non-CSCs to CSCs-like cells. Mechanistically, TAZ-TEADs binding and subsequent transcriptional activation of EMT mediators and pluripotency factors are presumably responsible for TAZ-mediated EMT and non-CSCs-to-CSCs conversion. Importantly, aberrant TAZ overexpression was found to be associated with tumor size, pathological grade and cervical lymph node metastasis, as well as unfavorable prognosis. Pharmacological repression of TAZ by simvastatin resulted in potent anti-cancer effects against OSCC. Taken together, our findings have revealed critical links between TAZ, EMT and CSCs in OSCC initiation and progression, and also established TAZ as a novel cancer biomarker and viable druggable target for OSCC therapeutics.
(Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: