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https://doi.org/10.1371/journal.pone.0026085
Title: | G12 signaling through c-jun nh 2-terminal kinase promotes breast cancer cell invasion | Authors: | Juneja, J. Cushman, I. Casey, P.J. |
Issue Date: | 7-Nov-2011 | Citation: | Juneja, J., Cushman, I., Casey, P.J. (2011-11-07). G12 signaling through c-jun nh 2-terminal kinase promotes breast cancer cell invasion. PLoS ONE 6 (11) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0026085 | Abstract: | Signaling through the heterotrimeric G protein, G12, via Rho induces a striking increase in breast cancer cell invasion. In this study, evidence is provided that the c-Jun NH 2-terminal kinase (JNK) is a key downstream effector of G12 on this pathway. Expression of constitutively-active Gα12 or activation of G12 signaling by thrombin leads to increased JNK and c-Jun phosphorylation. Pharmacologic inhibition of JNK or knockdown of JNK expression by siRNA significantly decreases G12-induced JNK activation as well as the ability of breast cancer cells to invade a reconstituted basement membrane. Furthermore, expression of dominant-negative Rho or treatment of cells with an inhibitor of the Rho kinase, ROCK, reduces G12-induced JNK and c-Jun activation, and ROCK inhibitor treatment also inhibits G12-induced cellular invasion. JNK knockdown or ROCK inhibitor treatment has no effect on activation of Rho by G12. Taken together, our data indicate that JNK activation is required for G12-induced invasion of breast cancer cells and that JNK is downstream of Rho and ROCK on this pathway. This study implicates a G12-stimulated mitogen-activated protein kinase cascade in cancer cell invasion, and supports a role for JNK in cancer progression. © 2011 Juneja et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | Source Title: | PLoS ONE | URI: | http://scholarbank.nus.edu.sg/handle/10635/110542 | ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0026085 |
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