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

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)39449-39459
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number47
DOIs
Publication statusPublished - Nov 16 2012

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Epithelial-Mesenchymal Transition
Cell Adhesion Molecules
Gene expression
Colonic Neoplasms
Tumors
Carcinogenesis
Gene Expression
Neoplasms
Genes
Amyloid Precursor Protein Secretases
Epithelial Cell Adhesion Molecule
Epithelial Cells
Tumor Suppressor Genes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Epithelial cell adhesion molecule regulates tumor initiation and tumorigenesis via activating reprogramming factors and epithelial-mesenchymal transition gene expression in colon cancer. / Lin, Cheng Wei; Liao, Mei Yin; Lin, Wen Wei; Wang, Yi Ping; Lu, Tung Yin; Wu, Han Chung.

In: Journal of Biological Chemistry, Vol. 287, No. 47, 16.11.2012, p. 39449-39459.

Research output: Contribution to journalArticle

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