A Jnk–Rho–Actin remodeling positive feedback network directs Src-driven invasion

Rudrapatna, V.A., Bangi, E. and Cagan, R.L. (2014) A Jnk–Rho–Actin remodeling positive feedback network directs Src-driven invasion. Oncogene, 33(21), pp. 2801-2806. (doi: 10.1038/onc.2013.232) (PMID:23831567)

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Abstract

Current models of tumor cell invasion propose that oncogenic signaling converges upon key orchestrators of cytoskeletal dynamics, including c-Jun N-terminal kinase (Jnk) and RhoGTPase family members; these signals dynamically direct Actin remodeling proteins (ARPs) to catalyze the cytoskeletal changes required for migration. Src is a key driver of tumor aggression, metastasis and patient mortality. To clarify how Src regulates Actin dynamics to promote invasive migration, we performed a genetic modifier screen in a Drosophila model of invasion. Nine genes linked to Actin dynamics were identified that mediate invasion in situ. We found that ARPs were required for many oncogenic effects of Src including Mmp1 expression and initiation of apoptosis. Surprisingly, they were also regulators of Jnk pathway activity: both Src and the small GTPase Rho1 activated Jnk in a manner dependent on ARPs during invasion. Our results suggest that ARPs are not simply downstream executors of signal transduction pathways. Rather, they participate in a positive feedback network involving canonical oncogenic signaling pathways that promote tumor invasion.

Item Type:Articles
Additional Information:VAR was supported by 5T32CA078207 and 5T32GM007280. This work was also supported by the National Institutes of Health grants NCI R01 CA109730 and 5R01EY011495.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cagan, Professor Ross
Authors: Rudrapatna, V.A., Bangi, E., and Cagan, R.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Oncogene
Publisher:Springer Nature
ISSN:0950-9232
ISSN (Online):1476-5594
Published Online:08 July 2013

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