Endothelin receptor type B counteracts tenascin-C-induced endothelin receptor type A-dependent focal adhesion and actin stress fiber disorganization
In: Cancer research (Baltimore), Jg. 67 (2007), Heft 13, S. 6163-6173
Online
academicJournal
- print, 40 ref
Zugriff:
Tenascin-C, an extracellular matrix molecule of the tumor-specific microenvironment, counteracts the tumor cell proliferation-suppressing effect of fibronectin by blocking the integrin α5β1/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 NH2-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.
Titel: |
Endothelin receptor type B counteracts tenascin-C-induced endothelin receptor type A-dependent focal adhesion and actin stress fiber disorganization
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Autor/in / Beteiligte Person: | LANGE, Katrin ; KAMMERER, Martial ; OREND, Gertraud ; HEGI, Monika E ; GROTEGUT, Stefan ; DITTMANN, Antje ; WENTAO, HUANG ; FLURI, Erika ; YIP, George W ; GÖTTE, Martin ; RUIZ, Christian |
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Zeitschrift: | Cancer research (Baltimore), Jg. 67 (2007), Heft 13, S. 6163-6173 |
Veröffentlichung: | Philadelphia, PA: American Association for Cancer Research, 2007 |
Medientyp: | academicJournal |
Umfang: | print, 40 ref |
ISSN: | 0008-5472 (print) |
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