Myocardin-related transcription factor A (MRTF-A) activity-dependent cell adhesion is correlated to focal adhesion kinase (FAK) activity.

Publisher: Impact Journals Country of Publication: United States NLM ID: 101532965 Publication Model: Print Cited Medium: Internet ISSN: 1949-2553 (Electronic) Linking ISSN: 19492553 NLM ISO Abbreviation: Oncotarget Subsets: MEDLINE

Original Publication: Albany, N.Y. : Impact Journals

Gene Expression Regulation, Neoplastic*; Focal Adhesion Kinase 1/*genetics ; Focal Adhesions/*pathology ; Neoplasms/*genetics ; Neoplasms/*pathology ; Trans-Activators/*metabolism; Actins/metabolism ; Animals ; Cell Adhesion/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Focal Adhesion Kinase 1/metabolism ; Humans ; Integrins/metabolism ; Mice ; Microscopy, Fluorescence ; Paxillin/metabolism ; Phosphorylation ; RNA Interference ; RNA, Small Interfering/metabolism ; Rats ; Real-Time Polymerase Chain Reaction ; Serum Response Factor/metabolism ; Signal Transduction/genetics ; Trans-Activators/genetics ; Up-Regulation ; src-Family Kinases/genetics ; src-Family Kinases/metabolism

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.

Cancer Res. 2005 Nov 1;65(21):9851-60. (PMID: 16267008)
Nat Cell Biol. 2015 Aug;17(8):955-63. (PMID: 26121555)
J Biol Chem. 1997 Oct 17;272(42):26643-51. (PMID: 9334246)
Nat Rev Drug Discov. 2010 Oct;9(10):804-20. (PMID: 20885411)
FEBS Lett. 2007 Aug 7;581(20):3777-82. (PMID: 17631293)
Curr Opin Cell Biol. 2006 Oct;18(5):516-23. (PMID: 16919435)
J Cell Sci. 1993 Feb;104 ( Pt 2):595-606. (PMID: 8505382)
Mol Cancer Ther. 2007 Aug;6(8):2249-60. (PMID: 17699722)
Nat Cell Biol. 2009 May;11(5):557-68. (PMID: 19350017)
Cell Adh Migr. 2012 Jul-Aug;6(4):302-6. (PMID: 22983197)
J Biol Chem. 2008 Nov 7;283(45):31183-96. (PMID: 18772142)
Nucleic Acids Res. 2016 Jan 4;44(D1):D710-6. (PMID: 26687719)
Oncol Res. 2011;19(7):335-48. (PMID: 21936403)
Nat Rev Mol Cell Biol. 2010 May;11(5):353-65. (PMID: 20414257)
Cell. 2003 May 2;113(3):329-42. (PMID: 12732141)
Exp Cell Res. 2007 Oct 1;313(16):3432-45. (PMID: 17714703)
Nat Rev Cancer. 2003 May;3(5):362-74. (PMID: 12724734)
Trends Pharmacol Sci. 2001 Jan;22(1):32-9. (PMID: 11165670)
Biochim Biophys Acta. 2007 Jun;1775(2):263-73. (PMID: 17292556)
Mol Biol Cell. 2007 Mar;18(3):1083-97. (PMID: 17215519)
Cell Cycle. 2009 Nov 1;8(21):3474-9. (PMID: 19829089)
J Cell Sci. 2011 Dec 15;124(Pt 24):4318-31. (PMID: 22223881)
Oncogene. 2002 Jun 6;21(25):3969-77. (PMID: 12037679)
J Biol Chem. 1996 Jan 26;271(4):2071-5. (PMID: 8567661)
J Cell Biol. 2007 Dec 3;179(5):1027-42. (PMID: 18056415)
Oncogene. 2001 Oct 1;20(44):6459-72. (PMID: 11607845)
J Cell Sci. 2009 Jan 15;122(Pt 2):199-206. (PMID: 19118212)
Nat Rev Cancer. 2014 Sep;14(9):598-610. (PMID: 25098269)
World J Gastroenterol. 2002 Aug;8(4):613-8. (PMID: 12174366)
Oncogene. 1999 Mar 18;18(11):2027-31. (PMID: 10208425)
Trends Cell Biol. 2006 Nov;16(11):588-96. (PMID: 17035020)
Nat Rev Mol Cell Biol. 2010 Nov;11(11):802-14. (PMID: 20966971)
Cancer Metastasis Rev. 2010 Mar;29(1):223-37. (PMID: 20112053)
Nat Rev Mol Cell Biol. 2005 Jan;6(1):56-68. (PMID: 15688067)
Cell Adh Migr. 2013 Mar-Apr;7(2):199-213. (PMID: 23302954)
Pathol Res Pract. 2013 Feb 15;209(2):105-9. (PMID: 23261238)
Carcinogenesis. 2010 Jul;31(7):1185-93. (PMID: 20338973)
Am J Pathol. 2002 Jul;161(1):183-93. (PMID: 12107103)
Histopathology. 1994 Mar;24(3):249-56. (PMID: 7515372)
Nat Cell Biol. 2009 Mar;11(3):257-68. (PMID: 19198601)
Cell Motil Cytoskeleton. 1992;22(2):127-34. (PMID: 1633623)
Nat Rev Mol Cell Biol. 2014 Dec;15(12):802-12. (PMID: 25355505)
Cancer Res. 2010 Jan 15;70(2):501-11. (PMID: 20068148)
Cell. 1995 Apr 7;81(1):53-62. (PMID: 7536630)

Keywords: cell adhesion; focal adhesion kinase; myocardin-related transcription factor; tumor cell migration

0 (Actins)
0 (Integrins)
0 (MRTFA protein, human)
0 (Mrtfa protein, mouse)
0 (PXN protein, human)
0 (Paxillin)
0 (RNA, Small Interfering)
0 (Serum Response Factor)
0 (Trans-Activators)
EC 2.7.10.2 (Focal Adhesion Kinase 1)
EC 2.7.10.2 (PTK2 protein, human)
EC 2.7.10.2 (Ptk2 protein, mouse)
EC 2.7.10.2 (src-Family Kinases)

Date Created: 20161007 Date Completed: 20180223 Latest Revision: 20200728

20231215

PMC5342149

10.18632/oncotarget.12350

27708220