Maria Teresa Herrera Abreu

Gab2 is as a proto-oncogene product that is overexpressed in breast cancer and has been shown to increase cell proliferation and reduce growth factor requirements. Additionally, Gab2 plays a role in cancer metastasis. However, the underlying mechanisms are unclear. My data show that Gab2 overexpression in MCF-10A mammary epithelial cells inhibits the formation of stress fibers, mature focal adhesions and cell-cell contacts. Interestingly, a Gab2 mutant that is uncoupled from 14-3-3 mediated negative feedback exhibited enhancement of migratory potential and acquired the ability to invade through Matrigel. Analysis of Rho GTPase activation in spreading and resting cells over-expressing Gab2 or the Gab22xA mutant revealed reduced RhoA activation. Currently, I am using Gab22xA and other Gab2 mutants (∆SHP2, ∆p85, ∆Grb2) to better characterize the molecular mechanisms underpinning Gab2- induced metastatic spread.