Epithelial cell adhesion molecule regulates tumor initiation and tumorigenesis via activating reprogramming factors and epithelial-mesenchymal transition gene expression in colon cancer

Cheng Wei Lin, Mei Yin Liao, Wen Wei Lin, Yi Ping Wang, Tung Yin Lu, Han Chung Wu

研究成果: 雜誌貢獻文章

68 引文 斯高帕斯(Scopus)

摘要

Epithelial cell adhesion molecule (EpCAM) is highly expressed in epithelial-transformed neoplasia and tumor-initiated cells (TICs), but the role that EpCAM plays in the stemness properties of TICs is still unclear. Here we show that EpCAM and reprogramming factors (c-Myc, Oct4, Nanog, and Sox2) were concomitantly elevated in TICs, which were shown to have superior self-renewal, invasiveness, and tumor-initiating abilities. Elevation of EpCAM enhanced tumorsphere formation and tumor initiation. Knockdown of EpCAM inhibited the expressions of reprogramming factors and epithelial-mesenchymal transition genes, thereby suppressing tumor initiation, self-renewal, and invasiveness. In addition, EpCAM, especially intracellular domain of EpCAM (EpICD), bound to and activated the promoter of reprogramming factors. Treatment with the inhibitor of γ-secretase (DAPT) led to the blockage of the expressions of reprogramming factors and epithelial-mesenchymal transition genes, which was accompanied by the reduction of tumor self-renewal and invasion. Furthermore, the increased release of EpEX enhanced production of EpICD and regulated the expression of reprogramming factors. Together, these findings suggest that EpCAM plays an important role in regulating cancer-initiating abilities in TICs of colon cancer. This discovery can be used in the development of new strategies for cancer therapy.

原文英語
頁(從 - 到)39449-39459
頁數11
期刊Journal of Biological Chemistry
287
發行號47
DOIs
出版狀態已發佈 - 十一月 16 2012

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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