title: Molecular pathways: P-Rex in cancer.
abstract: P-Rex proteins are Rho/Rac guanine nucleotide exchange factors that participate in the regulation of several cancer-related cellular functions such as proliferation, motility, and invasion. Expectedly, a significant portion of these actions of P-Rex proteins must be related to their Rac regulatory properties. In addition, P-Rex proteins control signaling by the phosphoinositide 3-kinase (PI3K) route by interacting with PTEN and mTOR. The interaction with PTEN inhibits its phosphatase activity, leading to AKT activation. The interaction with mTOR may be important in nutrient-stimulated Rac activation and migration. In humans, several studies have implicated P-Rex proteins in the pathophysiology of various neoplasias. Thus, overexpression of P-Rex proteins has been linked to poor patient outcome in breast cancer and may facilitate metastatic dissemination of prostate cancer cells. In addition, whole-genome sequencing described P-Rex2 as a significantly mutated gene in melanoma. Furthermore, expression in melanocytes of mutated forms of P-Rex2 found in patients with melanoma showed the protumorigenic role of these P-Rex mutations in melanoma genesis. These findings open interesting opportunities for P-Rex targeting in cancer. Moreover, the implication of P-Rex partner proteins such as Rac, mTOR, or PTEN in cancer has opened the possibility of acting on P-Rex to restrict protumorigenic signaling through these pathways.
authors.affiliation: Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer, CSIC-Universidad de Salamanca, Spain. atanasio@usal.es
authors.forename: Atanasio
authors.initials: A
authors.lastname: Pandiella
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Montero
mesh_terms: D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D053492:Elafin / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D053492:Elafin; D020662:Guanine Nucleotide Exchange Factors; C506806:PI3 protein, human; C490712:PREX2 protein, human; C546842:MTOR protein, human; D051058:Oncogene Protein v-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human