Kinase-Independent Functions of MASTL in Cancer: A New Perspective on MASTL Targeting

Cells. 2020 Jul 6;9(7):1624. doi: 10.3390/cells9071624.

Abstract

Microtubule-associated serine/threonine kinase-like (MASTL; Greatwall) is a well-characterized kinase, whose catalytic role has been extensively studied in relation to cell-cycle acceleration. Importantly, MASTL has been implicated to play a substantial role in cancer progression and subsequent studies have shown that MASTL is a significant regulator of the cellular actomyosin cytoskeleton. Several kinases have non-catalytic properties, which are essential or even sufficient for their functions. Likewise, MASTL functions have been attributed both to kinase-dependent phosphorylation of downstream substrates, but also to kinase-independent regulation of the actomyosin contractile machinery. In this review, we aimed to highlight the catalytic and non-catalytic roles of MASTL in proliferation, migration, and invasion. Further, we discussed the implications of this dual role for therapeutic design.

Keywords: MASTL; actin; cancer; cell cycle; contractility; kinase inhibitor; therapeutic targeting.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*

Substances

  • Actins
  • Microtubule-Associated Proteins
  • MASTL protein, human
  • Protein Serine-Threonine Kinases