Endothelin receptor type B counteracts tenascin-C-induced endothelin receptor type A-dependent focal adhesion and actin stress fiber disorganization

Details

Serval ID
serval:BIB_EE9455C4ED47
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Endothelin receptor type B counteracts tenascin-C-induced endothelin receptor type A-dependent focal adhesion and actin stress fiber disorganization
Journal
Cancer Research
Author(s)
Lange  K., Kammerer  M., Hegi  M. E., Grotegut  S., Dittmann  A., Huang  W., Fluri  E., Yip  G. W., Gotte  M., Ruiz  C., Orend  G.
ISSN
0008-5472 (Print)
Publication state
Published
Issued date
07/2007
Volume
67
Number
13
Pages
6163-73
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jul 1
Abstract
Tenascin-C, an extracellular matrix molecule of the tumor-specific microenvironment, counteracts the tumor cell proliferation-suppressing effect of fibronectin by blocking the integrin alpha(5)beta(1)/syndecan-4 complex. This causes cell rounding and stimulates tumor cell proliferation. Tenascin-C also stimulates endothelin receptor type A (EDNRA) expression. Here, we investigated whether signaling through endothelin receptors affects tenascin-C-induced cell rounding. We observed that endothelin receptor type B (EDNRB) activation inhibited cell rounding by tenascin-C and induced spreading by restoring expression and function of focal adhesion kinase (FAK), paxillin, RhoA, and tropomyosin-1 (TM1) via activation of epidermal growth factor receptor, phospholipase C, c-Jun NH(2)-terminal kinase, and the phosphatidylinositol 3-kinase pathway. In contrast to EDNRB, signaling through EDNRA induced cell rounding, which correlated with FAK inhibition and TM1 and RhoA protein destabilization in the presence of tenascin-C. This occurred in a mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-dependent manner. Thus, tumorigenesis might be enhanced by tenascin-C involving EDNRA signaling. Inhibition of tenascin-C in combination with blocking both endothelin receptors could present a strategy for sensitization of cancer and endothelial cells toward anoikis.
Keywords
Actins/*metabolism Brain Neoplasms/metabolism Cell Adhesion Cell Proliferation Cytoskeleton/metabolism Focal Adhesions *Gene Expression Regulation, Neoplastic Glioma/metabolism Humans Kinetics Receptor, Endothelin A/metabolism/*physiology Receptor, Endothelin B/metabolism/*physiology Signal Transduction Stress Fibers/metabolism Tenascin/*biosynthesis/metabolism
Pubmed
Web of science
Create date
25/01/2008 14:06
Last modification date
20/08/2019 17:16
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