EGFR Signals through a DOCK180-MLK3 Axis to Drive Glioblastoma Cell Invasion

In this study, evidence is provided that MLK3 is essential for GBM cell migration and invasion, and that an MLK inhibitor blocks EGF-induced migration and invasion. MLK3 silencing or MLK inhibition blocks EGF-induced JNK activation, suggesting that MLK3-JNK signaling promotes invasion of GBM cells. Mechanistically, it is demonstrated that DOCK180, a RAC1 guanine nucleotide exchange factor (GEF) overexpressed in invasive GBM cells, activates the MLK3-JNK signaling axis in a RAC1-dependent manner. In summary, this investigation identifies an EGFR–DOCK180–RAC1–MLK3–JNK signaling axis that drives glioblastoma cell migration and dissemination. Implications: On the basis of these findings, MLK3 emerges as a potential therapeutic target for the treatment of glioblastoma. Mol Cancer Res; 15(8); 1085–95. ©2017 AACR.

http://mcr.aacrjournals.org/cgi/content/short/15/8/1085?rss=1

Source: Molecular Cancer Research - August 1, 2017 Category: Cancer & Oncology Authors: Misek, S. A., Chen, J., Schroeder, L., Rattanasinchai, C., Sample, A., Sarkaria, J. N., Gallo, K. A. Tags: Signal Transduction Source Type: research