Tags

Type your tag names separated by a space and hit enter

MASTL promotes cell contractility and motility through kinase-independent signaling.
J Cell Biol. 2020 Jun 01; 219(6)JC

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.

Authors+Show Affiliations

Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, and Center for Integrative Biological Signalling Studies, Freiburg, Germany.Cancer Research UK Beatson Institute, Glasgow, UK.Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, and Center for Integrative Biological Signalling Studies, Freiburg, Germany.Cancer Research UK Beatson Institute, Glasgow, UK. Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.Cancer Research UK Beatson Institute, Glasgow, UK. Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland. Department of Biochemistry, University of Turku, Turku, Finland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32311005

Citation

Taskinen, Maria Emilia, et al. "MASTL Promotes Cell Contractility and Motility Through Kinase-independent Signaling." The Journal of Cell Biology, vol. 219, no. 6, 2020.
Taskinen ME, Närvä E, Conway JRW, et al. MASTL promotes cell contractility and motility through kinase-independent signaling. J Cell Biol. 2020;219(6).
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., Norman, J. C., & Ivaska, J. (2020). MASTL promotes cell contractility and motility through kinase-independent signaling. The Journal of Cell Biology, 219(6). https://doi.org/10.1083/jcb.201906204
Taskinen ME, et al. MASTL Promotes Cell Contractility and Motility Through Kinase-independent Signaling. J Cell Biol. 2020 Jun 1;219(6) PubMed PMID: 32311005.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MASTL promotes cell contractility and motility through kinase-independent signaling. AU - Taskinen,Maria Emilia, AU - Närvä,Elisa, AU - Conway,James R W, AU - Hinojosa,Laura Soto, AU - Lilla,Sergio, AU - Mai,Anja, AU - De Franceschi,Nicola, AU - Elo,Laura L, AU - Grosse,Robert, AU - Zanivan,Sara, AU - Norman,Jim C, AU - Ivaska,Johanna, PY - 2019/06/28/received PY - 2020/02/03/revised PY - 2020/03/11/accepted PY - 2020/12/01/pmc-release PY - 2020/4/21/entrez PY - 2020/4/21/pubmed PY - 2020/4/21/medline JF - The Journal of cell biology JO - J. Cell Biol. VL - 219 IS - 6 N2 - 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. SN - 1540-8140 UR - https://www.unboundmedicine.com/medline/citation/32311005/MASTL_promotes_cell_contractility_and_motility_through_kinase_independent_signaling_ L2 - https://rupress.org/jcb/article-lookup/doi/10.1083/jcb.201906204 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.