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
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
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