title: FAK tyrosine 407 organized with integrin αVβ5 in Hs578Ts(i)8 advanced triple-negative breast cancer cells.
abstract: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase known to promote cell migration and invasiveness. Overexpression and increased activity of FAK are closely associated with metastatic breast tumors and are linked to poor prognosis. This study discovered an inverse correlation between FAK activity and migratory and invasive behavior. We show decreased phosphorylation levels of FAK at tyrosine residues 397 and 861, and most prominently at Y407, in the more invasive Hs578Ts(i)8 subclone of the Hs578T breast cancer progression model. There is limited information available on FAK Y407, and here we demonstrate its presence in triple-negative breast cancer (TNBC) cell lines. Furthermore, our studies propose that localization of FAK Y407, rather than FAK expression and overall FAK Y407 phosphorylation levels, is crucial for the control of cell motility. FAK Y407 is found extensively at the cell periphery in focal adhesion-like structures at each end of actin stress fibers and organized with integrin αVβ5 receptors, linking the αVβ5 integrin-mediated migratory behavior of Hs578Ts(i)8 cells to FAK Y407. These data suggest that subcellular localization, next to expression and activity levels, are important for understanding TNBC progression. Such an approach opens new avenues for further studies and may provide novel insight for the classification of TNBC and facilitate the discovery of effective biomarkers for diagnosis and therapy of TNBC.
authors.affiliation: School of Science, Technology and Engineering Management, St. Thomas University, Miami Gardens, FL 33054, USA.
authors.forename: Iliet
authors.initials: I
authors.lastname: Payan
authors.affiliation: UCD School of Chemical and Bioprocess Engineering, University College Dublin, Belfield Dublin 4, Ireland.
authors.forename: Susan
authors.initials: S
authors.lastname: McDonnell
authors.affiliation: Department of Chemistry and Biochemistry, South Dakota State University, Brookings, SD 57007, USA.
authors.forename: Haydee M
authors.initials: HM
authors.lastname: Torres
authors.affiliation: School of Science, Technology and Engineering Management, St. Thomas University, Miami Gardens, FL 33054, USA.
authors.forename: Wim F A
authors.initials: WF
authors.lastname: Steelant
authors.affiliation: School of Science, Technology and Engineering Management, St. Thomas University, Miami Gardens, FL 33054, USA.
authors.forename: Séverine
authors.initials: S
authors.lastname: Van Slambrouck
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D019030:Receptors, Vitronectin / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D014443:Tyrosine; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human