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

J Pathol. 2014 Sep;234(1):99-107. doi: 10.1002/path.4383. Epub 2014 Jul 23.


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.

Keywords: Oct4; Wnt/β-catenin signalling; cancer stem cells; head and neck cancer; target therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / therapy
  • Cell Dedifferentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic*
  • Head and Neck Neoplasms / pathology*
  • Head and Neck Neoplasms / therapy
  • Humans
  • Neoplastic Stem Cells / pathology*
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism*
  • RNA, Small Interfering / genetics
  • Squamous Cell Carcinoma of Head and Neck
  • Stem Cells / metabolism
  • Stem Cells / pathology
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / genetics*
  • beta Catenin / genetics
  • beta Catenin / metabolism


  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • RNA, Small Interfering
  • Wnt Proteins
  • beta Catenin