Medical College of Wisconsin
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EpCAM-Regulated Transcription Exerts Influences on Nanomechanical Properties of Endometrial Cancer Cells That Promote Epithelial-to-Mesenchymal Transition. Cancer Res 2016 Nov 01;76(21):6171-6182

Date

11/03/2016

Pubmed ID

27569206

Pubmed Central ID

PMC5405773

DOI

10.1158/0008-5472.CAN-16-0752

Scopus ID

2-s2.0-84995543447 (requires institutional sign-in at Scopus site)   47 Citations

Abstract

Overexpression of epithelial cell adhesion molecule (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 cell-surface 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 EpCAM-regulated transcription and altered biophysical properties of cells that promote EMT in advanced endometrial cancer. Cancer Res; 76(21); 6171-82. ©2016 AACR.

Author List

Hsu YT, Osmulski P, Wang Y, Huang YW, Liu L, Ruan J, Jin VX, Kirma NB, Gaczynska ME, Huang TH

Author

Victor X. Jin PhD Professor in the Data Science Institute department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Biomechanical Phenomena
Cell Line, Tumor
Cell Nucleus
Endometrial Neoplasms
Epidermal Growth Factor
Epithelial Cell Adhesion Molecule
Epithelial-Mesenchymal Transition
Female
Gene Editing
Humans
Lymphoid Enhancer-Binding Factor 1
Microscopy, Atomic Force
Tight Junctions
Transcription, Genetic