The CREB coactivator CRTC2 promotes oncogenesis in LKB1-mutant non–small cell lung cancer

Laura Rodón, Robert U. Svensson, Ezra Wiater, Matthew G.H. Chun, Wen Wei Tsai, Lillian J. Eichner, Reuben J. Shaw, Marc Montminy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


The LKB1 tumor suppressor is often mutationally inactivated in non–small cell lung cancer (NSCLC). LKB1 phosphorylates and activates members of the AMPK family of Ser/Thr kinases. Within this family, the salt-inducible kinases (SIKs) modulate gene expression in part via the inhibitory phosphorylation of the CRTCs, coactivators for CREB (cAMP response element-binding protein). The loss of LKB1 causes SIK inactivation and the induction of the CRTCs, leading to the up-regulation of CREB target genes. We identified CRTC2 as a critical factor in LKB1-deficient NSCLC. CRTC2 is unphosphorylated and therefore constitutively activated in LKB1-mutant NSCLC, where it promotes tumor growth, in part via the induction of the inhibitor of DNA binding 1 (ID1), a bona fide CREB target gene. As ID1 expression is up-regulated and confers poor prognosis in LKB1-deficient NSCLC, our results suggest that small molecules that inhibit CRTC2 and ID1 activity may provide therapeutic benefit to individuals with NSCLC.

Original languageEnglish (US)
Article numbereaaw6455
JournalScience Advances
Issue number7
StatePublished - Jul 24 2019
Externally publishedYes

ASJC Scopus subject areas

  • General


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