Taskinen, M. E. et al. (2020) MASTL promotes cell contractility and motility through kinase-independent signaling. Journal of Cell Biology, 219(6), e20190620. (doi: 10.1083/jcb.201906204) (PMID:32311005) (PMCID:PMC7265322)
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Abstract
Microtubule-associated serine/threonine-protein kinase-like (MASTL) is a mitosis-accelerating kinase with emerging roles in cancer progression. However, possible cell cycle-independent mechanisms behind its oncogenicity remain ambiguous. Here, we identify MASTL as an activator of cell contractility and MRTF-A/SRF (myocardin-related transcription factor A/serum response factor) signaling. Depletion of MASTL increased cell spreading while reducing contractile actin stress fibers in normal and breast cancer cells and strongly impairing breast cancer cell motility and invasion. Transcriptome and proteome profiling revealed MASTL-regulated genes implicated in cell movement and actomyosin contraction, including Rho guanine nucleotide exchange factor 2 (GEF-H1, ARHGEF2) and MRTF-A target genes tropomyosin 4.2 (TPM4), vinculin (VCL), and nonmuscle myosin IIB (NM-2B, MYH10). Mechanistically, MASTL associated with MRTF-A and increased its nuclear retention and transcriptional activity. Importantly, MASTL kinase activity was not required for regulation of cell spreading or MRTF-A/SRF transcriptional activity. Taken together, we present a previously unknown kinase-independent role for MASTL as a regulator of cell adhesion, contractility, and MRTF-A/SRF activity. [Abstract copyright: © 2020 Taskinen et al.]
Item Type: | Articles |
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Additional Information: | This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). This study was supported by the Academy of Finland (E. Närvä grant 297079 and J. Ivaska grant 312517), the Academy of Finland CoE for Translational Cancer Biology (J. Ivaska), the European Research Council CoG grant 615258 (J. Ivaska), the Sigrid Juselius Foundation (J. Ivaska), the Finnish Cancer Organization (J. Ivaska and E. Närvä), Cancer Research UK (grants A17196 and A12935 to S. Lilla and S. Zanivan), and the Wilhelm-Sander Foundation (grant 2013.149.2 to R. Grosse). M.E. Taskinen has been supported by the University of Turku Doctoral Program for Molecular Medicine. J.R.W. Conway has been supported by the European Union’s Horizon 2020 research and innovation program under Marie Sklodowska-Curie grant agreement 841973. We also acknowledge EMBO for a short-term fellowship (E. Närvä). |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Lilla, Dr Sergio and Norman, Professor James and Zanivan, Professor Sara |
Creator Roles: | |
Authors: | Taskinen, M. E., Närvä, E., Conway, J. R. W., Hinojosa, L. S., Lilla, S., Mai, A., De Franceschi, N., Elo, L. L., Grosse, R., Zanivan, S. R., Norman, J. C., and Ivaska, J. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
Journal Name: | Journal of Cell Biology |
Publisher: | Rockefeller University Press |
ISSN: | 1540-8140 |
ISSN (Online): | 1540-8140 |
Published Online: | 20 April 2020 |
Copyright Holders: | Copyright © 2020 Taskinen et al. |
First Published: | First published in Journal of Cell Biology 2019(6):e20190620 |
Publisher Policy: | Reproduced under a Creative Commons licence |
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