Activation of the integrin effector kinase focal adhesion kinase in cancer cells is regulated by crosstalk between protein kinase Cα and the PDZ adapter protein mda-9/syntenin

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dc.contributor.authorC Hwangbo-
dc.contributor.authorJ Kim-
dc.contributor.authorJung Joon Lee-
dc.contributor.authorJ H Lee-
dc.date.accessioned2017-04-19T09:17:29Z-
dc.date.available2017-04-19T09:17:29Z-
dc.date.issued2010-
dc.identifier.issn0008-5472-
dc.identifier.uri10.1158/0008-5472.CAN-09-2447ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/9428-
dc.description.abstractAberrant adhesion signaling pathways in cancer cells underlie their deadly invasive capabilities. The adhesion-related PDZ adapter protein mda-9/syntenin is a positive regulator of cancer cell progression in breast cancer, melanoma, and other human cancers. In this study, we report that mda-9/syntenin mediates adhesion-mediated activation of protein kinase Cα (PKCα) and focal adhesion kinase (FAK) by fibronectin (FN) in human breast cancer and melanoma cells. FN rapidly stimulated the expression of mda-9/syntenin and the activation of PKCα prior to activation of FAK. Inhibiting PKCα suppressed basal or FN-induced expression of mda-9/syntenin, as well as cell migration and invasion toward FN stimulated by mda-9/syntenin. Several lines of evidence suggested that activation of PKCα and expression of mda-9/syntenin were interdependent. First, mda-9/syntenin inhibition suppressed basal or FN-induced phosphorylation of PKCα at Thr638/641, whereas PKCα inhibition suppressed basal or FN-induced expression of mda-9/syntenin. Second, inhibiting either mda-9/syntenin or PKCα suppressed FN-induced formation of integrin-β1/FAK/c-Src signaling complexes. Third, inhibiting either mda-9/syntenin or PKCα suppressed FN-induced phosphorylation of FAK Tyr397 and c-Src Tyr416 and the induction of downstream effector signals to p38 and mitogen-activated protein kinase, Cdc42, and NF-κB. In summary, our findings offer evidence that mda-9/syntenin acts as a molecular adaptor linking PKCα and FAK activation in a pathway of FN adhesion by human breast cancer and melanoma cells.-
dc.publisherAmer Assoc Cancer Research-
dc.titleActivation of the integrin effector kinase focal adhesion kinase in cancer cells is regulated by crosstalk between protein kinase Cα and the PDZ adapter protein mda-9/syntenin-
dc.title.alternativeActivation of the integrin effector kinase focal adhesion kinase in cancer cells is regulated by crosstalk between protein kinase Cα and the PDZ adapter protein mda-9/syntenin-
dc.typeArticle-
dc.citation.titleCancer Research-
dc.citation.number4-
dc.citation.endPage1655-
dc.citation.startPage1645-
dc.citation.volume70-
dc.contributor.affiliatedAuthorJung Joon Lee-
dc.contributor.alternativeName황보철-
dc.contributor.alternativeName김재경-
dc.contributor.alternativeName이정준-
dc.contributor.alternativeName이정형-
dc.identifier.bibliographicCitationCancer Research, vol. 70, no. 4, pp. 1645-1655-
dc.identifier.doi10.1158/0008-5472.CAN-09-2447-
dc.description.journalClassY-
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