Wnt/β‐catenin signalling maintains self‐renewal and tumourigenicity of head and neck squamous cell carcinoma stem‐like cells by activating Oct4

Citations Over TimeTop 10% of 2014 papers

Abstract

Abstract 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.

Related Papers

• → Knockdown of LIMD2 inhibits the progression of ovarian carcinoma through ERK1/2 pathway(2023)2 cited
• → Knockdown of ecdysteroid synthesis genes results in impaired molting and high mortality in Bactericera cockerelli (Hemiptera: Triozidae)(2022)9 cited
• → Supplementary Revised Figure S3 from MUC16 Regulates TSPYL5 for Lung Cancer Cell Growth and Chemoresistance by Suppressing p53(2023)
• → Supplementary Revised Figure S4 from MUC16 Regulates TSPYL5 for Lung Cancer Cell Growth and Chemoresistance by Suppressing p53(2023)
• → Supplementary Revised Figure S3 from MUC16 Regulates TSPYL5 for Lung Cancer Cell Growth and Chemoresistance by Suppressing p53(2023)