Please use this identifier to cite or link to this item: 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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