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

Cited 71 time in scopus
Metadata Downloads
Title
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
Author(s)
C Hwangbo; J Kim; Jung Joon Lee; J H Lee
Bibliographic Citation
Cancer Research, vol. 70, no. 4, pp. 1645-1655
Publication Year
2010
Abstract
Aberrant 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.
ISSN
0008-5472
Publisher
Amer Assoc Cancer Research
DOI
http://dx.doi.org/10.1158/0008-5472.CAN-09-2447
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.