Myocardin-related transcription factor A (MRTF-A) activity-dependent cell adhesion is correlated to focal adhesion kinase (FAK) activity
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Takayuki Kishi1,2,*, Taira Mayanagi1,*, Sadahiro Iwabuchi1, Toshihide Akasaka2, Kenji Sobue1
1Department of Neuroscience, Institute for Biomedical Sciences, School of Medicine, Iwate Medical University, Yahaba 028-3694, Japan
2Department of Dermatology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan
*These authors have contributed equally to this work
Kenji Sobue, email: [email protected]
Keywords: cell adhesion, myocardin-related transcription factor, focal adhesion kinase, tumor cell migration
Received: April 26, 2016 Accepted: September 17, 2016 Published: September 30, 2016
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.
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