title: ARF1 regulates adhesion of MDA-MB-231 invasive breast cancer cells through formation of focal adhesions.
abstract: Adhesion complex formation and disassembly is crucial for maintaining efficient cell movement. During migration, several proteins act in concert to promote remodeling of the actin cytoskeleton and we have previously shown that in highly invasive breast cancer cells, this process is regulated by small GTP-binding proteins of the ADP-ribosylation factor (ARF) family. These are overexpressed and highly activated in these cells. Here, we report that one mechanism by which ARF1 regulates migration is by controlling assembly of focal adhesions. In cells depleted of ARF1, paxillin is no longer colocalized with actin at focal adhesion sites. In addition, we demonstrate that this occurs through the ability of ARF1 to regulate the recruitment of key proteins such as paxillin, talin and FAK to ß1-integrin. Furthermore, we show that the interactions between paxillin and talin together and with FAK are significantly impaired in ARF1 knocked down cells. Our findings also indicate that ARF1 is essential for EGF-mediated phosphorylation of FAK and Src. Finally, we report that ARF1 can be found in complex with key focal adhesion proteins such as ß1-integrin, paxillin, talin and FAK. Together our findings uncover a new mechanism by which ARF1 regulates cell migration and provide this GTPase as a target for the development of new therapeutics in triple negative breast cancer.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montreal, QC H3C 3J7, Canada.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schlienger
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montreal, QC H3C 3J7, Canada.
authors.forename: Rodrigo Alain Migueles
authors.initials: RA
authors.lastname: Ramirez
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montreal, QC H3C 3J7, Canada. Electronic address: audrey.claing@umontreal.ca.
authors.forename: Audrey
authors.initials: A
authors.lastname: Claing
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000814:Aniline Compounds / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016608:Talin / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D001562:Benzimidazoles; D019012:Integrin beta1; C521938:LM11 compound; D051419:Paxillin; D034741:RNA, Small Interfering; D016608:Talin; D004815:Epidermal Growth Factor; D051417:Focal Adhesion Kinase 1; D020823:ADP-Ribosylation Factor 1
keywords: ADP-ribosylation factor-1; Breast cancer; Epidermal growth factor receptor; Focal adhesion; Focal adhesion kinase