Figure 4.

CRTC1 activation drives the LKB1-null gene signature. A) Principle component analysis of LKB1-null gene expression signature. LKB1-mutant lung cancer cell lines (red) completely separate from LKB1-wt cell lines (blue) along the first principle component. Four outlier LKB1-wt cell lines (H292, H2170, H2342, EKVX) exhibited an LKB1-null gene expression pattern (yellow). These cell lines were identified and omitted prior to signature generation. Two EKVX replicates were included for quality control and exhibit high reproducibility. The outlier H292 cell line (arrow) expresses the endogenous activated CRTC1 fusion oncogene that is required for sustained tumor cell growth (1,31). B) The indicated top scoring drugs identified in the C-MAP screen that drive the LKB1-null signature are known cAMP/CRTC1 activators. Custom software, metadata tables, and CMAP differentially expressed gene lists used in the CMAP and E-MTAB-783 analyses (see Supplementary Methods, available online, for further details).