期刊
JOURNAL OF PATHOLOGY
卷 234, 期 1, 页码 99-107出版社
WILEY-BLACKWELL
DOI: 10.1002/path.4383
关键词
head and neck cancer; cancer stem cells; Wnt/beta-catenin signalling; Oct4; target therapy
资金
- National Research Foundation of Korea (NRF) - Korean Government (MEST) [2010-0022256, 2012R1A2A2A01046214]
- Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A111700]
- Korea Health Promotion Institute [A111700] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2010-0022256, 2012R1A2A2A01046214] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Accumulating evidence suggests that a distinct subpopulation of cancer stem cells (CSCs) is responsible for tumour initiation and progression in head and neck squamous cell carcinoma (HNSCC). Wnt/beta-catenin signalling is essential for stem cell regulation and tumourigenesis, but its molecular mechanism in HNSCC CSCs remains unknown. We investigated whether Wnt/beta-catenin signalling regulates self-renewal and tumourigenicity of HNSCC stem-like cells in vitro and in vivo. Cytoplasmic/nuclear beta-catenin, a major effector of Wnt/beta-catenin signalling, was expressed in a subpopulation of tumour cells in primary HNSCC tissue but in none of normal head and neck tissues. Overexpression of beta-catenin increased proliferation of HNSCC cells and induced dedifferentiation of these cells to cells with stem-like features. Knockdown of beta-catenin in HNSCC stem-like cells blocked their self-renewal capacity, stemness-associated gene expression, chemoresistance, and in vivo tumourigenicity. Furthermore, beta-catenin directly regulates Oct4 transcription in HNSCC stem-like cells. In addition, the effect of shRNA-mediated repression of beta-catenin on CSC traits in HNSCC stem-like cells was reversed by overexpression of Oct4. In patients with HNSCC, higher levels of both cytoplasmic/nuclear beta-catenin and Oct4 correlated with the worst prognosis. These results suggest inhibition of Wnt/beta-catenin signalling as a novel therapeutic strategy for targeting HNSCC stem-like cells. Copyright (C) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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