Myosin IIA suppresses glioblastoma development in a mechanically sensitive manner
Abstract
Glioblastoma, the most common and lethal of primary brain tumors, can diffusely infiltrate brain. Because the components of the cytoskeleton that drive tumor invasion are nonredundant, they have been attractive targets for blocking glioblastoma dispersion. However, we find that while targeting one of these—the molecular motor myosin IIA—effectively blocks glioblastoma invasion, it enhances tumor proliferation and lethality. In this study, we have found that myosin IIA functions as a tumor suppressor by reducing signaling of two oncogenes—ERK1/2 and NF-κB—in a manner regulated by the mechanics of the tumor and surrounding brain. Our results also argue that effective treatment of glioblastoma will require inhibiting targets that drive both invasion and proliferation.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 24, 2019
- Source ID
- 10.1073/pnas.1902847116
Entities
People
- Amanda Luu
- Athanassios Dovas
- David J. Odde
- Emily S. Bell
- Hannah S. Picariello
- James F. Crish
- Jan Lammerding
- Katarzyna Pogoda
- Mariah Mcmahon
- Paul A. Janmey
- Peter Canoll
- Rajappa S. Kenchappa
- Rita West
- Steven S. Rosenfeld
- Thomas Egelhoff
- Unnikrishnan Chandrasekharan
- Vandana Rai
Organizations
- Cleveland Clinic
- Columbia University
- Cornell University
- Mayo Clinic
- National Cancer Center
- National Cancer Institute
- National Heart, Lung, and Blood Institute
- National Institute of General Medical Sciences
- National Institute of Neurological Disorders and Stroke
- National Science Foundation
- Polish Academy of Sciences
- United States Department of Defense
- University of Minnesota
- University of Pennsylvania