Research ArticleCancer

Phosphorylation of FADD by the kinase CK1α promotes KRASG12D-induced lung cancer

See allHide authors and affiliations

Science Signaling  27 Jan 2015:
Vol. 8, Issue 361, pp. ra9
DOI: 10.1126/scisignal.2005607

This article has a correction. Please see:

Conversion of a death adaptor to a proliferation mediator

Activating mutations in the protein RAS drive cell proliferation and tumor growth. Although best known for mediating cell death signaling through its death domain, when phosphorylated, the adaptor protein FADD promotes cell survival and proliferation. Bowman et al. found that, compared with KRAS mutant mice, KRAS mutant mice engineered to lack FADD or its upstream kinase CK1α developed fewer lung tumors. Lung tissue and cells from KRAS mutant mice had increased abundance of CK1α, phosphorylated FADD, and proliferative markers. In lung tumor samples from patients, expression of FADD was greater in tumors that had mutant KRAS. A CK1α inhibitor prevented FADD from physically interacting with mitotic kinases and suppressed cell proliferation in culture. Thus, blocking the phosphorylation of FADD may be a new strategy for patients with KRAS mutant lung tumors.

View Full Text

Stay Connected to Science Signaling