The epithelial-mesenchymal transition mediator S100A4 maintains cancer-initiating cells in head and neck cancers

Jeng Fan Lo*, Cheng Chia Yu, Shih Hwa Chiou, Chih Yang Huang, Chia Ing Jan, Shu Chun Lin, Chung Ji Liu, Wen Yuan Hu, Yau Hua Yu

*此作品的通信作者

研究成果: Article同行評審

115 引文 斯高帕斯(Scopus)

摘要

Cancer-initiating cells (CIC) comprise a rare subpopulation of cells in tumors that are proposed to be responsible for tumor growth. Starting from CICs identified in head and neck squamous cell carcinomas (HNSCC), termed head and neck cancer-initiating cells (HN-CIC), we determined as a candidate stemnessmaintaining molecule for HN-CICs the proinflammatory mediator S100A4, which is also known to be an inducer of epithelial-mesenchymal transition. S100A4 knockdown in HN-CICs reduced their self-renewal capability and their stemness and tumorigenic properties, both in vitro and in vivo. Conversely, S100A4 overexpression in HNSCC cells enhanced their stem cell properties. Mechanistic investigations indicated that attenuation of endogenous S100A4 levels in HNSCC cells caused downregulation of Notch2 and PI3K (phosphoinositide 3-kinase)/pAKT along with upregulation of PTEN, consistent with biological findings. Immunohistochemical analysis of HNSCC clinical specimens showed that S100A4 expression was positively correlated with clinical grading, stemness markers, and poorer patient survival. Together, our findings reveal a crucial role for S100A4 signaling pathways in maintaining the stemness properties and tumorigenicity of HN-CICs. Furthermore, our findings suggest that targeting S100A4 signaling may offer a new targeted strategy for HNSCC treatment by eliminating HN-CICs.

原文English
頁(從 - 到)1912-1923
頁數12
期刊Cancer Research
71
發行號5
DOIs
出版狀態Published - 1 3月 2011

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