Myosin 10 Regulates Invasion, Mitosis, and Metabolic Signaling in Glioblastoma

Rajappa S. Kenchappa, Panagiotis Mistriotis, Emily Wisniewski, Santanu Bhattacharya, Tanmay Kulkarni, Rita West, Amanda Luu, Meghan Conlon, Ernest Heimsath, James F. Crish, Hannah S. Picariello, Athanassios Dovas, Natanael Zarco, Montserrat Lara-Velazquez, Alfredo Quinones-Hinojosa, John A. Hammer, Debrabrata Mukhopadhyay, Richard E. Cheney, Konstantinos Konstantopoulos, Peter CanollSteven S. Rosenfeld

Research output: Contribution to journalArticlepeer-review

Abstract

Invasion and proliferation are defining phenotypes of cancer, and in glioblastoma blocking one stimulates the other, implying that effective therapy must inhibit both, ideally through a single target that is also dispensable for normal tissue function. The molecular motor myosin 10 meets these criteria. Myosin 10 knockout mice can survive to adulthood, implying that normal cells can compensate for its loss; its deletion impairs invasion, slows proliferation, and prolongs survival in murine models of glioblastoma. Myosin 10 deletion also enhances tumor dependency on the DNA damage and the metabolic stress responses and induces synthetic lethality when combined with inhibitors of these processes. Our results thus demonstrate that targeting myosin 10 is active against glioblastoma by itself, synergizes with other clinically available therapeutics, may have acceptable side effects in normal tissues, and has potential as a heretofore unexplored therapeutic approach for this disease.

Original languageEnglish (US)
Article number101802
JournaliScience
Volume23
Issue number12
DOIs
StatePublished - Dec 18 2020

Keywords

  • Cancer
  • Cell Biology

ASJC Scopus subject areas

  • General

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