Baseline expression of c-Myc defines the tissue specificity of oncogenic K-Ras
Popow, O.; Yu, Q.; Yapp, C.; Hull, S.; Paulo, J. A.; Hanna, B.; Xu, S.; Kuang, Y.; Sigel, C.; Paweletz, C. P.; Gygi, S. P.; Haigis, K. M.
Show abstract
KRAS is among the most frequently mutated oncogenes in cancer. Yet, mutations in KRAS are common only in tumors originating from a subset of tissues. It is critical to understand the molecular mechanisms underlying this oncogene tissue specificity. Utilizing genetically engineered mouse models carrying a conditional oncogenic allele of Kras, we expressed activated K-Ras in adult tissues to investigate its specificity. We discovered that the ability of K-RasG12D to influence the fitness of cells in a given tissue is not determined by its canonical signaling through MAPK. Instead, low baseline expression of c-Myc renders tissues non-permissive to oncogenic K-Ras, a context that can be reversed in the liver by ectopically expressing c-Myc. This functions independently of the proliferative index of the tissue or the induction of cell cycle arrest or apoptosis. Our findings reveal the importance of the basal state of the tissue-inherent signaling network for determining oncogene specificity.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- p120 RasGAP and ZO-2 are essential for Hippo signaling and tumor suppressor function mediated by p190A RhoGAP 95%
- SF3B1 promotes tumor malignancy through splicing-independent co-activation of HIF1α 95%
- Recruitment of BAG2 to DNAJ-PKAc scaffolds promotes cell survival and resistance to drug-induced apoptosis in fibrolamellar carcinoma 95%
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.