MASTL promotes cell contractility and motility through kinase-independent signaling

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

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
Journal of cell biology. - 219, 6 (2020) , e201906204, ISSN: 1540-8140

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2020
Creator
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

DOI
10.1083/jcb.201906204
URN
urn:nbn:de:bsz:25-freidok-1670811
Rights
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Last update
14.08.2025, 10:54 AM CEST

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Associated

  • 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
  • Universität

Time of origin

  • 2020

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