@article{10902/7100,
year = {2014},
month = {9},
url = {http://hdl.handle.net/10902/7100},
abstract = {The small GTPase Cdc42 is a key regulator of polarity, but little is known in mammals about its spatial regulation and the relevance of spatial Cdc42 pools for polarity. Here we report the identification of a GM130-RasGRF complex as a regulator of Cdc42 at the Golgi. Silencing GM130 results in RasGRF-dependent inhibition of the Golgi pool of Cdc42, but does not affect Cdc42 at the cell surface. Furthermore, active Cdc42 at the Golgi is important to sustain asymmetric front-rear Cdc42-GTP distribution in directionally migrating cells. Concurrent to Cdc42 inhibition, silencing GM130 also results in RasGRF-dependent Ras-ERK pathway activation. Moreover, depletion of GM130 is sufficient to induce E-cadherin downregulation, indicative of a loss in cell polarity and epithelial identity. Accordingly, GM130 expression is frequently lost in colorectal and breast cancer patients. These findings establish a previously unrecognized role for a GM130-RasGRF-Cdc42 connection in regulating polarity and tumorigenesis.},
publisher = {Nature Publishing Group},
publisher = {Nature Communications. 2014 Sep 11;5:4839},
title = {Spatial control of Cdc42 signalling by a GM130-RasGRF complex regulates polarity and tumorigenesis},
author = {Baschieri, Francesco and Confalonieri, Stefano and Bertalot, Giovanni and Fiore, Pier Paolo Di and Dietmaier, Wolfgang and Leist, Marcel and Crespo Baraja, Piero and Macara, Ian G. and Farhan, Hesso},
}