Critical requirement of SOS1 for tumor development and microenvironment modulation in KRAS-driven lung adenocarcinoma.

The impact of genetic ablation of SOS1 or SOS2 is evaluated in a murine model of KRAS-driven lung adenocarcinoma (LUAD). SOS2 ablation shows some protection during early stages but only SOS1 ablation causes significant, specific long term increase of survival/lifespan of the KRAS mice associated to markedly reduced tumor burden and reduced populations of cancer-associated fibroblasts, macrophages and T-lymphocytes in the lung tumor microenvironment (TME). SOS1 ablation also causes specific shrinkage and regression of LUAD tumoral masses and components of the TME in pre-established KRAS LUAD tumors.

Advances in Molecular Research of Oncogenes.

The isolation of the first human oncogene (HRAS), a critical breakthrough in cancer research, has occurred over forty years ago, and the identification of new pathogenic oncogenes has continuously grown since [...

Critical Requirement of SOS1 for Development of BCR/ABL-Driven Chronic Myelogenous Leukemia.

We showed previously that the ABL-mediated phosphorylation of SOS1 promotes RAC activation and contributes to BCR-ABL leukemogenesis, suggesting the relevant role of SOS1 in the pathogenesis of CML. To try and obtain direct experimental evidence of the specific mechanistic implication of SOS1 in CML development, here, we combined a murine model of CML driven by a p210 transgene with our tamoxifen-inducible SOS1/2-KO system in order to investigate the phenotypic impact of the direct genetic ablation of SOS1 or SOS2 on the pathogenesis of CML. Our observations showed that, in contrast to control animals expressing normal levels of SOS1 and SOS2 or to single SOS2-KO mice, p210 transgenic mice devoid of SOS1 presented significantly extended survival curves and also displayed an almost complete disappearance of the typical hematological alterations and splenomegaly constituting the hallmarks of CML.