The MEK5–ERK5 Kinase Axis Controls Lipid Metabolism in Small-Cell Lung Cancer
Abstract
Small-cell lung cancer (SCLC) is an aggressive form of lung cancer with dismal survival rates. While kinases often play key roles driving tumorigenesis, there are strikingly few kinases known to promote the development of SCLC. Here, we investigated the contribution of the MAPK module MEK5–ERK5 to SCLC growth. MEK5 and ERK5 were required for optimal survival and expansion of SCLC cell lines in vitro and in vivo. Transcriptomics analyses identified a role for the MEK5–ERK5 axis in the metabolism of SCLC cells, including lipid metabolism. In-depth lipidomics analyses showed that loss of MEK5/ERK5 perturbs several lipid metabolism pathways, including the mevalonate pathway that controls cholesterol synthesis. Notably, depletion of MEK5/ERK5 sensitized SCLC cells to pharmacologic inhibition of the mevalonate pathway by statins. These data identify a new MEK5–ERK5–lipid metabolism axis that promotes the growth of SCLC.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 13, 2020
- Source ID
- 10.1158/0008-5472.can-19-1027
Entities
People
- Alexandros P. Drainas
- Andrew He
- Daniel Hornburg
- Garry L. Coles
- Julia Arand
- Julien Sage
- Jun W. Kim
- Kévin Contrepois
- Lauren Averett Byers
- Laurent Le Cam
- Maya Gershkovitz
- Michael P. Snyder
- Sandra Cristea
- Siqi Cao
- Stuart Williamson
- Triparna Sen
Organizations
- National Institutes of Health
- Stanford University
- United States Department of Defense
- University of Montpellier
- University of Texas at Austin