Here, for the first time, we document that deltarasin produces both apoptosis and autophagy in KRAS-dependent lung cancer cells in vitro and inhibits lung tumor growth in vivo.
We show that initiation and progression of KRAS-driven lung tumors require input from ERBB family receptor tyrosine kinases (RTKs): Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS-driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRAS<sup>G12D</sup>-driven lung tumors.
The Kras mutational spectra of chemically induced lung tumors in different inbred mice mimics the spectra of KRAS mutations in adenocarcinomas in smokers versus nonsmokers.
Heterozygous inactivation of TGF-beta1 increases the susceptibility to chemically induced mouse lung tumorigenesis independently of mutational activation of K-ras.
KRAS coding exons in 61 treatment-naive colorectal cancer (CRC) tumors and KRAS, EGFR, ALK, and MET in lung tumors from three Chinese non-small cell lung cancer (NSCLC) patients were sequenced using ultradeep sequencing methods.
Based on published studies showing that oncogenic RAS promotes angiogenesis by upregulating the proangiogenic NF-κB target genes IL-8 and VEGF, that NF-κB activation by KRAS requires the IKKβ kinase, and that targeting IKKβ reduces KRAS-induced lung tumor growth in vivo, but has limited effects on cell growth in vitro, we hypothesized that IKKβ targeting would reduce lung tumor growth by inhibiting KRAS-induced angiogenesis.
K-ras mutations in lung tumors and tumors from other organs are consistent with a common mechanism of ethylene oxide tumorigenesis in the B6C3F1 mouse.
We propose that the Pas1 modifier effect is due to Kras2, and that a sensitive balance between the expression levels of wild-type and mutant alleles determines lung tumor susceptibility.
Enhancement of lung carcinogenesis initiated with 4-(N-hydroxymethylnitrosamino)-1-(3-pyridyl)-1-butanone by Ogg1 gene deficiency in female, but not male, mice.
Map kinase activation correlates with K-ras mutation and loss of heterozygosity on chromosome 6 in alveolar bronchiolar carcinomas from B6C3F1 mice exposed to vanadium pentoxide for 2 years.
CASC1, which is frequently co-amplified with KRAS in lung tumors, is essential for microtubule polymerization and satisfaction of the spindle assembly checkpoint.
Decrease in K-ras p21 and increase in Raf1 and activated Erk 1 and 2 in murine lung tumors initiated by N-nitrosodimethylamine and promoted by 2,3,7,8-tetrachlorodibenzo-p-dioxin.