Cavin-3 (PRKCDBP, hSRBC) is a tumor suppressor protein that is commonly absent in epithelial cancers (carcinomas), particularly late in disease progression. Frequency of loss in primary tumors ranges from 50 percent to 80 percent, depending on cancer type.
Our work has shown that cavin-3 dictates the balance between ERK and Akt signaling: increases in cavin-3 function increase ERK activity over Akt, while loss of cavin-3 function increases Akt activity over ERK.
The cellular consequences of cavin-3 loss include Warburg metabolism (aerobic glycolysis), rapid cell proliferation, and resistance to cell death (apoptosis).
Whole-body cavin-3 knockout in mice increases Akt signaling and glycolytic metabolism in the tissues, among other effects. Animals die prematurely of cachexia, a wasting syndrome characterized by severe lipodystrophy and muscle loss.
A role for cavin-3 as a bulwark against cachexia is consistent with the observation that cancers with high incidence of cancer-associated cachexia (CAC) are the cancers that most commonly lack cavin-3 expression.
We are currently investigating how loss of cavin-3 causes cachexia. CAC is the immediate cause of death in 20 percent of all cancer patients, and at least half of all cancer patients experience some level of cachexia.
- Hernandez VJ, Weng J, Ly P, Pompey S, Dong H, Mishra L, Schwarz M, Anderson RG, Michaely P. Cavin-3 dictates the balance between ERK and Akt signaling. Elife. 2013 2:e00905. PMID: 24069528.