Helmholtz Gemeinschaft


Multiomic characterization of oncogenic signaling mediated by wild-type and mutant RIT1

Item Type:Article
Title:Multiomic characterization of oncogenic signaling mediated by wild-type and mutant RIT1
Creators Name:Lo, A. and Holmes, K. and Kamlapurkar, S. and Mundt, F. and Moorthi, S. and Fung, I. and Fereshetian, S. and Watson, J. and Carr, S.A. and Mertins, P. and Berger, A.H.
Abstract:Aberrant activation of the RAS family of guanosine triphosphatases (GTPases) is prevalent in lung adenocarcinoma, with somatic mutation of KRAS occurring in ~30% of tumors. We previously identified somatic mutations and amplifications of the gene encoding RAS family GTPase RIT1 in lung adenocarcinomas. To explore the biological pathways regulated by RIT1 and how they relate to the oncogenic KRAS network, we performed quantitative proteomic, phosphoproteomic, and transcriptomic profiling of isogenic lung epithelial cells in which we ectopically expressed wild-type or cancer-associated variants of RIT1 and KRAS. We found that both mutant KRAS and mutant RIT1 promoted canonical RAS signaling and that overexpression of wild-type RIT1 partially phenocopied oncogenic RIT1 and KRAS, including induction of epithelial-to-mesenchymal transition. Our findings suggest that RIT1 protein abundance is a factor in its pathogenic function. Therefore, chromosomal amplification of wild-type RIT1 in lung and other cancers may be tumorigenic.
Keywords:Oncogenes, Signal Transduction, ras Proteins
Source:Science Signaling
Publisher:American Association for the Advancement of Science
Page Range:eabc4520
Date:30 November 2021
Official Publication:https://doi.org/10.1126/scisignal.abc4520
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library