Id-1 promotes TGF-beta1-induced cell motility through HSP27 activation and disassembly of adherens junction in prostate epithelial cells.
Id-1 (inhibitor of differentiation or DNA binding-1) has been positively associated with cell proliferation, cell cycle progression, and invasiveness during tumorigenesis. In addition, Id-1 has been shown to modulate cellular sensitivity to TGF-beta1 (transforming growth factor beta1). Here we demonstrate a novel role of Id-1 in promoting TGF-beta1-induced cell motility in a non-malignant prostate epithelial cell line, NPTX. We found that Id-1 promoted F-actin stress fiber formation in response to TGF-beta1, which was associated with increased cell-substrate adhesion and cell migration in NPTX cells. In addition, this positive effect of Id-1 on TGF-beta1-induced cell motility was mediated through activation of MEK-ERK signaling pathway and subsequent phosphorylation of HSP27 (heat shock protein 27). Furthermore, Id-1 disrupted the adherens junction complex in TGF-beta1-treated cells through down-regulation of E-cadherin, redistribution of beta-catenin, along with up-regulation of N-cadherin. These lines of evidence reveal a novel tumorigenic role of Id-1 through reorganization of actin cytoskeleton and disassembly of cell-cell adhesion in response to TGF-beta1 in human prostate epithelial cells, and suggest that intracellular Id-1 levels might be a determining factor for switching TGF-beta1 from a growth inhibitor to a tumor promoter during prostate carcinogenesis.
Di
Kaijun
K
Cancer Biology Group, Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Wong
Yong Chuan
YC
Wang
Xianghong
X
D022005:Adherens Junctions / Q000648:ultrastructure*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D004847:Epithelial Cells / Q000166:cytology; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D008297:Male; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism*; D011467:Prostate / Q000166:cytology*; D022502:Stress Fibers; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
D015820:Cadherins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D051798:Inhibitor of Differentiation Protein 1; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D053773:Transforming Growth Factor beta1