title: Myocardin-related transcription factor A (MRTF-A) activity-dependent cell adhesion is correlated to focal adhesion kinase (FAK) activity.
abstract: The regulation of cell-substrate adhesion is tightly linked to the malignant phenotype of tumor cells and plays a role in their migration, invasion, and metastasis. Focal adhesions (FAs) are dynamic adhesion structures that anchor the cell to the extracellular matrix. Myocardin-related transcription factors (MRTFs), co-regulators of the serum response factor (SRF), regulate expression of a set of genes encoding actin cytoskeletal/FA-related proteins. Here we demonstrated that the forced expression of a constitutively active MRTF-A (CA-MRTF-A) in B16F10 melanoma cells induced the up-regulation of actin cytoskeletal and FA proteins, resulting in FA reorganization and the suppression of cell migration. Expression of CA-MRTF-A markedly increased phosphorylation of focal adhesion kinase (FAK) and paxillin, which are important components for FA dynamics. Notably, FAK activation was triggered by the clustering of up-regulated integrins. Our results revealed that the MRTF-SRF-dependent regulation of cell migration requires both the up-regulation of actin cytoskeletal/FA proteins and the integrin-mediated regulation of FA components via the FAK/Src pathway. We also demonstrated that activation of the MRTF-dependent transcription correlates FAK activation in various tumor cells. The elucidation of the correlation between MRTF and FAK activities would be an effective therapeutic target in focus of tumor cell migration.
authors.affiliation: Department of Neuroscience, Institute for Biomedical Sciences, School of Medicine, Iwate Medical University, Yahaba 028-3694, Japan.|Department of Dermatology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kishi
authors.affiliation: Department of Neuroscience, Institute for Biomedical Sciences, School of Medicine, Iwate Medical University, Yahaba 028-3694, Japan.
authors.forename: Taira
authors.initials: T
authors.lastname: Mayanagi
authors.affiliation: Department of Neuroscience, Institute for Biomedical Sciences, School of Medicine, Iwate Medical University, Yahaba 028-3694, Japan.
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Iwabuchi
authors.affiliation: Department of Dermatology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Akasaka
authors.affiliation: Department of Neuroscience, Institute for Biomedical Sciences, School of Medicine, Iwate Medical University, Yahaba 028-3694, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sobue
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D051417:Focal Adhesion Kinase 1 / Q000235:genetics* / Q000378:metabolism; D022001:Focal Adhesions / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016023:Integrins / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D026362:Serum Response Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D016023:Integrins; C431575:MRTFA protein, human; C511173:Mrtfa protein, mouse; C496061:PXN protein, human; D051419:Paxillin; D034741:RNA, Small Interfering; D026362:Serum Response Factor; D015534:Trans-Activators; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse; D019061:src-Family Kinases
keywords: cell adhesion; focal adhesion kinase; myocardin-related transcription factor; tumor cell migration