RT Journal Article T1 Rac signaling in breast cancer: A tale of GEFs and GAPs A1 Wertheimer, Eva A1 Gutiérrez Uzquiza, Álvaro A1 Rosemblit, Cinthia A1 Lopez-Haber, Cynthia A1 Sosa, Maria Soledad A1 Kazanietz, Marcelo G. AB Rac GTPases, small G-proteins widely implicated in tumorigenesis and metastasis, transduce signals from tyrosine-kinase, G-protein-coupled receptors (GPCRs), and integrins, and control a number of essential cellular functions including motility, adhesion, and proliferation. Deregulation of Rac signaling in cancer is generally a consequence of enhanced upstream inputs from tyrosine-kinase receptors, PI3K or Guanine nucleotide Exchange Factors (GEFs), or reduced Rac inactivation by GTPase Activating Proteins (GAPs). In breast cancer cells Rac1 is a downstream effector of ErbB receptors and mediates migratory responses by ErbB1/EGFR ligands such as EGF or TGFα and ErbB3 ligands such as heregulins. Recent advances in the field led to the identification of the Rac-GEF P-Rex1 as an essential mediator of Rac1 responses in breast cancer cells. P-Rex1 is activated by the PI3K product PIP3 and Gβγ subunits, and integrates signals from ErbB receptors and GPCRs. Most notably, P-Rex1 is highly overexpressed in human luminal breast tumors, particularly those expressing ErbB2 and estrogen receptor (ER). The P-Rex1/Rac signaling pathway may represent an attractive target for breast cancer therapy. PB Elsevier SN 0898-6568 YR 2012 FD 2012-02 LK https://hdl.handle.net/20.500.14352/93505 UL https://hdl.handle.net/20.500.14352/93505 LA eng NO Wertheimer E, Gutierrez-Uzquiza A, Rosemblit C, Lopez-Haber C, Sosa MS, Kazanietz MG. Rac signaling in breast cancer: A tale of GEFs and GAPs. Cellular Signalling 2012;24:353–62. https://doi.org/10.1016/j.cellsig.2011.08.011. NO Susan G. Komen for the Cure (M.G.K.) NO National Institutes of Health (NIH) DS Docta Complutense RD 6 abr 2025