Unbiased proteomic profiling uncovers a targetable GNAS/PKA/PP2A axis in SCLC

ABSTRACT: 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, inhibits SCLC expansion in culture and in vivo. Conversely, GNAS (G-protein α subunit), a PKA activator that is genetically activated in a small subset of human SCLC, promotes SCLC development. Phosphoproteomic analyses identified many new PKA substrates and mechanisms of action. In particular, PKA activity is required for the propagation of SCLC cancer stem cells in transplantation studies. Broad proteomic analysis of recalcitrant cancers has the potential to uncover novel targetable signaling networks, such as the GNAS/PKA/PP2A axis in SCLC.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Lung Neuroendocrine Cell, Lung

DISEASE(S): Pulmonary Neuroendocrine Tumor

SUBMITTER: John Gordan  

LAB HEAD: John Gordan

PROVIDER: PXD018209 | Pride | 2020-06-17

REPOSITORIES: Pride