期刊
CANCER CELL
卷 38, 期 1, 页码 129-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2020.05.003
关键词
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资金
- NCI [1U24CA213274]
- American Cancer Society postdoctoral fellowship
- Department of Defense [W81XWH-15-10250]
- Emerson Collective
- Lung Cancer Research Foundation
- Burroughs Wellcome Fund Career award
- NSF (GRFP award)
- Stanford Graduate Fellowship in Science and Engineering
- NIH [1S10OD016229-0, CA209891, CA181654, CA240993, ES028096, CA244255, CA201513, 4CA217450]
- Samuel Waxman Cancer Research Foundation
- Howard Hughes Medical Institute
Using unbiased kinase profiling, we identified protein kinase A (PKA) as an active kinase in small cell lung cancer (SCLC). Inhibition of PKA activity genetically, or pharmacologically by activation of the PP2A phosphatase, suppresses SCLC expansion in culture and in vivo. Conversely, GNAS (G-protein alpha subunit), a PKA activator that is genetically activated in a small subset of human SCLC, promotes SCLC development. Phosphoproteomic analyses identified many PKA substrates and mechanisms of action. In particular, PKA activity is required for the propagation of SCLC stem cells in transplantation studies. Broad proteomic analysis of recalcitrant cancers has the potential to uncover targetable signaling networks, such as the GNAS/PKA/PP2A axis in SCLC.
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