MASTL promotes cell contractility and motility through kinase-independent signaling

• Published in: The Journal of cell biology Vol. 219; no. 6; p. 1
• Main Authors: Taskinen, Maria Emilia, Närvä, Elisa, Conway, James R W, Hinojosa, Laura Soto, Lilla, Sergio, Mai, Anja, De Franceschi, Nicola, Elo, Laura L, Grosse, Robert, Zanivan, Sara, Norman, Jim C, Ivaska, Johanna
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 01-06-2020
• Subjects: Actin; Actin Cytoskeleton - enzymology; Actin Cytoskeleton - genetics; Actin Cytoskeleton - metabolism; Actomyosin; Breast cancer; Cancer; Cell adhesion; Cell adhesion & migration; Cell Adhesion - genetics; Cell cycle; Cell Cycle - genetics; Cell Line, Tumor; Cell Movement - genetics; Cell Nucleus - metabolism; Cell spreading; Contractility; Contraction; Cytoskeleton; Depletion; Fibers; Gene expression; Gene Expression Profiling; Genes; Guanine; Guanine nucleotide exchange factor; Humans; Integrins - genetics; Integrins - metabolism; Kinases; Microtubule-Associated Proteins - deficiency; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Mitosis; Motility; Myosin; Nonmuscle Myosin Type IIB - genetics; Nonmuscle Myosin Type IIB - metabolism; Nucleotides; Phosphorylation; Protein Binding; Protein kinase; Protein Serine-Threonine Kinases - deficiency; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Proteome - metabolism; Proteomes; Rho Guanine Nucleotide Exchange Factors - genetics; Rho Guanine Nucleotide Exchange Factors - metabolism; RNA, Small Interfering; Serum response factor; Signal Transduction - genetics; Signaling; Stress Fibers - genetics; Stress Fibers - metabolism; Threonine; Trans-Activators - genetics; Trans-Activators - metabolism; Transcriptome - genetics; Tropomyosin; Tropomyosin - genetics; Tropomyosin - metabolism; Vinculin; Vinculin - genetics; Vinculin - metabolism
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/JCB.201906204

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.