EpCAM-regulated transcription exerts influences on nanomechanical properties of endometrial cancer cells that promote epithelial-to-mesenchymal transition

Ya Ting Hsu, Pawel Osmulski, Yao Wang, Yi Wen Huang, Lu Liu, Jianhua Ruan, Victor X Jin, Nameer B Kirma, Maria E Gaczynska, Hui-ming Huang

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Overexpression of epithelial cell adhesionmolecule (EpCAM) has been implicated in advanced endometrial cancer, but its roles in this progression remain to be elucidated. In addition to its structural role in modulating cell-surface adhesion, here we demonstrate that EpCAM is a regulatory molecule in which its internalization into the nucleus turns on a transcription program. Activation of EGF/EGFR signal transduction triggered cellsurface cleavage of EpCAM, leading to nuclear internalization of its cytoplasmic domain EpICD. ChIP-seq analysis identified target genes that are coregulated by EpICD and its transcription partner, LEF-1. Network enrichment analysis further uncovered a group of 105 genes encoding functions for tight junction, adherent, and cell migration. Furthermore, nanomechanical analysis by atomic force microscopy revealed increased softness and decreased adhesiveness of EGF-stimulated cancer cells, implicating acquisition of an epithelial-mesenchymal transition (EMT) phenotype. Thus, genome editing of EpCAM could be associated with altering these nanomechanical properties towards a less aggressive phenotype. Using this integrative genomic-biophysical approach, we demonstrate for the first time an intricate relationship between EpCAMregulated transcription and altered biophysical properties of cells that promote EMT in advanced endometrial cancer.

Original languageEnglish (US)
Pages (from-to)6171-6182
Number of pages12
JournalCancer Research
Volume76
Issue number21
DOIs
Publication statusPublished - Nov 1 2016

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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