title: Cdc42 regulates Cdc42EP3 function in cancer-associated fibroblasts.
abstract: Rho family GTPases such as Cdc42 are key regulators of essential cellular processes through their effects on cytoskeletal dynamics, signaling and gene expression. Rho GTPases modulate these functions by engaging a wide variety of downstream effectors. Among these effectors is the largely understudied Cdc42EP/BORG family of Cdc42 effectors. BORG proteins have been linked to actin and septin regulation, but their role in development and disease is only starting to emerge. Recently, Cdc42EP3/BORG2 was shown to coordinate actin and septin cytoskeleton rearrangements in cancer-associated fibroblasts (CAFs). Interestingly, Cdc42EP3 expression potentiated cellular responses to mechanical stimulation leading to signaling and transcriptional adaptations required for the emergence of a fully activated CAF phenotype. These findings uncover a novel role for the BORG/septin network in cancer. Here, we demonstrate that Cdc42EP3 function in CAFs relies on tight regulation by Cdc42.
authors.affiliation: a Tumour Microenvironment Team, Division of Cancer Biology , Institute of Cancer Research , London , UK.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Farrugia
authors.affiliation: a Tumour Microenvironment Team, Division of Cancer Biology , Institute of Cancer Research , London , UK.
authors.forename: Fernando
authors.initials: F
authors.lastname: Calvo
mesh_terms: D000199:Actins / Q000378:metabolism; D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism*; D020555:GTP-Binding Protein Regulators / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D058112:Septins / Q000378:metabolism; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; C484093:CDC42EP3 protein, human; D020555:GTP-Binding Protein Regulators; D058112:Septins; D020764:cdc42 GTP-Binding Protein
keywords: BORG; Cdc42EP3; Rho GTPases; cancer-associated fibroblasts; cytoskeleton; septin