Id-1 induces cell invasiveness in immortalized epithelial cells by regulating cadherin switching and Rho GTPases

Epithelial‐mesenchymal transition (EMT), characterized by cadherin switching, contributes to cancer metastasis. Our recent study showed that Id‐1 (inhibitor of differentiation‐1) promotes metastasis in esophageal cancer cells, but whether the invasive and metastatic dynamics can be induced early in...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cellular biochemistry 2011-01, Vol.112 (1), p.157-168
Main Authors: Cheung, P.Y., Yip, Y.L., Tsao, S.W., Ching, Y.P., Cheung, A.L.M.
Format: Article
Language:English
Subjects:
Cadherins - metabolism
Cell Differentiation
Cell Movement
EMT
Epithelial Cells - cytology
Epithelial Cells - metabolism
Epithelial-Mesenchymal Transition
esophageal
HeLa Cells
Humans
Id-1
Inhibitor of Differentiation Protein 1 - metabolism
invasiveness
N-cadherin
rho GTP-Binding Proteins - metabolism
Rho GTPases
Signal Transduction
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Epithelial‐mesenchymal transition (EMT), characterized by cadherin switching, contributes to cancer metastasis. Our recent study showed that Id‐1 (inhibitor of differentiation‐1) promotes metastasis in esophageal cancer cells, but whether the invasive and metastatic dynamics can be induced early in the carcinogenesis process is still unclear. Immortalization is regarded as the initial stage in the malignant transformation of normal cells. In this study, we investigated the role and mechanisms of Id‐1 in inducing EMT and cell invasiveness in immortalized esophageal epithelial cells. We found that immortalized epithelial cells expressed higher endogenous levels of Id‐1 compared with normal cells. Ectopic Id‐1 expression inhibited the differentiation of immortalized esophageal epithelial cells and promoted cadherin switching, which was accompanied by increased adhesiveness to extracellular matrix, cell motility, migratory potential and matrix metalloproteinase‐dependent invasiveness. GTPase activity assays showed that over‐expression or short‐hairpin RNA knockdown of Id‐1 led to corresponding changes in Rac1 activity, whereas RhoA activity was significantly decreased with Id‐1 depletion. Inhibitors targeting Rac1, RhoA, and Rho kinase suppressed the invasiveness of Id‐1‐expressing NE2‐hTERT cells. Knockdown of N‐cadherin in Id‐1‐over‐expressing cells inhibited cell invasiveness and down‐regulated RhoA activity. These data suggest that the Id‐1‐induced invasive potential may be regulated through the N‐cadherin‐RhoA axis and Rac1 activation. J. Cell. Biochem. 112: 157–168, 2011. © 2010 Wiley‐Liss, Inc.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.22911