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Wnt/β‐catenin signalling maintains self‐renewal and tumourigenicity of head and neck squamous cell carcinoma stem‐like cells by activating Oct4
Author(s) -
Lee Sang Hyuk,
Koo Bon Seok,
Kim Jin Man,
Huang Songmei,
Rho Young Soo,
Bae Woo Jin,
Kang Hyun Jung,
Kim Young Sook,
Moon Jung Hwa,
Lim Young Chang
Publication year - 2014
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4383
Subject(s) - wnt signaling pathway , cancer stem cell , head and neck squamous cell carcinoma , stem cell , cancer research , catenin , biology , cancer , microbiology and biotechnology , signal transduction , head and neck cancer , genetics
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/β‐catenin signalling is essential for stem cell regulation and tumourigenesis, but its molecular mechanism in HNSCC CSCs remains unknown. We investigated whether Wnt/β‐catenin signalling regulates self‐renewal and tumourigenicity of HNSCC stem‐like cells in vitro and in vivo . Cytoplasmic/nuclear β‐catenin, a major effector of Wnt/β‐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 β‐catenin increased proliferation of HNSCC cells and induced dedifferentiation of these cells to cells with stem‐like features. Knockdown of β‐catenin in HNSCC stem‐like cells blocked their self‐renewal capacity, stemness‐associated gene expression, chemoresistance, and in vivo tumourigenicity. Furthermore, β‐catenin directly regulates Oct4 transcription in HNSCC stem‐like cells. In addition, the effect of shRNA ‐mediated repression of β‐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 β‐catenin and Oct4 correlated with the worst prognosis. These results suggest inhibition of Wnt/β‐catenin signalling as a novel therapeutic strategy for targeting HNSCC stem‐like cells. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.