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G12 signaling through JNK promotes breast cancer cell invasion
Author(s) -
Juneja Juhi,
Kelly Patrick,
Casey Patrick J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1044.1
Subject(s) - microbiology and biotechnology , heterotrimeric g protein , signal transduction , cancer research , gene knockdown , kinase , cell migration , chemistry , cancer cell , invadopodia , cell , biology , cancer , g protein , apoptosis , biochemistry , genetics
The G12 family of heterotrimeric G proteins has been implicated in such cellular processes as cytoskeletal rearrangements, cell‐cell adhesion and oncogenic transformation. Recently, work done in our laboratory has shown that G12 signaling via Rho induces a striking increase in breast cancer cell invasion in vitro and in vivo . In a continuation of this study, we further characterized G12 signaling leading to invasion of breast cancer cells. We show that c‐Jun N‐terminal kinase (JNK) is a key downstream effector of G12 on this pathway. Expression of constitutively active Gα12 leads to increased JNK and c‐Jun phosphorylation in the MDA‐MB‐231 breast cancer cell line. Chemical inhibition of JNK or knockdown of JNK by siRNA significantly decreases G12‐induced JNK activation as well as the ability of cells to invade Matrigel in in vit ro transwell invasion assays. Furthermore, treatment of these cells with the Rho kinase (ROCK) inhibitor reduces G12‐induced JNK and c‐Jun activation and also G12‐induced cellular invasion. JNK knockdown or ROCK inhibitor treatment has no effect on activation of Rho by G12. This suggests that a Rho‐ROCK‐JNK signaling axis is stimulated by G12 to promote breast cancer cell invasion. We are currently studying which G protein coupled receptor(s) G12 couples to in order to engage this pathway. This work was supported by a Human Frontier Science Program Fellowship (to J.J.).