TY - JOUR
T1 - Rac signaling in breast cancer
T2 - A tale of GEFs and GAPs
AU - Wertheimer, Eva
AU - Gutierrez-Uzquiza, Alvaro
AU - Rosemblit, Cinthia
AU - Lopez-Haber, Cynthia
AU - Sosa, Maria Soledad
AU - Kazanietz, Marcelo G.
N1 - Funding Information:
This work was supported by grants CA74197 , CA129133 , and CA139120 from NIH , and KG090522 from Susan G. Komen for the Cure (M.G.K.).
PY - 2012/2
Y1 - 2012/2
N2 - 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.
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.
KW - Breast cancer
KW - ErbB receptors
KW - GAPs
KW - GEFs
KW - P-Rex1
KW - Rac
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U2 - 10.1016/j.cellsig.2011.08.011
DO - 10.1016/j.cellsig.2011.08.011
M3 - Review article
C2 - 21893191
AN - SCOPUS:83555168297
SN - 0898-6568
VL - 24
SP - 353
EP - 362
JO - Cellular Signalling
JF - Cellular Signalling
IS - 2
ER -