Abstract IA16: The global proteome and phospho-proteome of K-Ras mutant tissues

Abstract

Abstract K-Ras is the most commonly mutated oncogene in cancer, and it plays a predominant role in the pathogenesis of cancers of the pancreas, colon, and lung. Mutationally activated K-Ras influences cellular behaviors through broad and complex effects on downstream signal transduction pathways. In an effort to understand the molecular mechanisms underlying the oncogenic properties of mutant forms of K-Ras, we have used multiplexed mass spectroscopy (MS) to quantify proteome-wide changes in protein phosphorylation in primary mouse tissues that are engineered to express mutant K-Ras, either alone or in combination with mutations in other cancer genes. This multidimensional dataset highlights the context dependence of K-Ras signaling because the significant changes in protein abundance and/or phosphorylation due to activation of K-Ras are highly dependent upon both tissue context and cooperating mutations. The dataset also paints a complex picture of signaling downstream of K-Ras within a given tissue, as phosphorylation of many proteins in known Ras effector pathways (i.e., MAPK and PI3K) are unaffected or downregulated by mutationally activated K-Ras. Overall, this study provides an unprecedented view of K-Ras signaling on a global scale and reveals a variety of novel insights into the signal transduction properties of mutant K-Ras alleles. Citation Format: Kevin Haigis. The global proteome and phospho-proteome of K-Ras mutant tissues [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr IA16.