title: FAK competes for Src to promote migration against invasion in melanoma cells.
abstract: Melanoma is one of the most deadly cancers because of its high propensity to metastasis, a process that requires migration and invasion of tumor cells driven by the regulated formation of adhesives structures like focal adhesions (FAs) and invasive structures like invadopodia. FAK, the major kinase of FAs, has been implicated in many cellular processes, including migration and invasion. In this study, we investigated the role of FAK in the regulation of invasion. We report that suppression of FAK in B16F10 melanoma cells led to increased invadopodia formation and invasion through Matrigel, but impaired migration. These effects are rescued by FAK WT but not by FAK(Y397F) reexpression. Invadopodia formation requires local Src activation downstream of FAK and in a FAK phosphorylation-dependant manner. FAK deletion correlates with increased phosphorylation of Tks-5 (tyrosine kinase substrate with five SH3 domain) and reactive oxygen species production. In conclusion, our data show that FAK is able to mediate opposite effects on cell migration and invasion. Accordingly, beneficial effects of FAK inhibition are context dependent and may depend on the cell response to environmental cues and/or on the primary or secondary changes that melanoma experienced through the invasion cycle.
authors.affiliation: 1] CNRS, UMR 7213, Laboratoire de Biophotonique et Pharmacologie, Illkirch, France [2] Université de Strasbourg, Faculté de Pharmacie, Illkirch, France.
authors.forename: K
authors.initials: K
authors.lastname: Kolli-Bouhafs
authors.affiliation: 1] CNRS, UMR 7213, Laboratoire de Biophotonique et Pharmacologie, Illkirch, France [2] Université de Strasbourg, Faculté de Pharmacie, Illkirch, France.
authors.forename: E
authors.initials: E
authors.lastname: Sick
authors.affiliation: 1] CNRS, UMR 7213, Laboratoire de Biophotonique et Pharmacologie, Illkirch, France [2] Université de Strasbourg, Faculté de Pharmacie, Illkirch, France.
authors.forename: F
authors.initials: F
authors.lastname: Noulet
authors.affiliation: 1] CNRS, UMR 7213, Laboratoire de Biophotonique et Pharmacologie, Illkirch, France [2] Université de Strasbourg, Faculté de Pharmacie, Illkirch, France.
authors.forename: J-P
authors.initials: JP
authors.lastname: Gies
authors.affiliation: 1] CNRS, UMR 7213, Laboratoire de Biophotonique et Pharmacologie, Illkirch, France [2] Université de Strasbourg, Faculté de Pharmacie, Illkirch, France.
authors.forename: J
authors.initials: J
authors.lastname: De Mey
authors.affiliation: 1] CNRS, UMR 7213, Laboratoire de Biophotonique et Pharmacologie, Illkirch, France [2] Université de Strasbourg, Faculté de Pharmacie, Illkirch, France.
authors.forename: P
authors.initials: P
authors.lastname: Rondé
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D028044:Phosphate-Binding Proteins; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C412373:AG 1879; C114235:Fish protein, mouse; D008665:Metalloporphyrins; C502230:Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; D028044:Phosphate-Binding Proteins; D010750:Phosphoproteins; D011743:Pyrimidines; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D019061:src-Family Kinases