Transcriptional and metabolic rewiring of colorectal cancer cells expressing the oncogenic KRASG13D mutation

Menée sur quatre lignées cellulaires de cancer colorectal, cette étude met en évidence une modification du programme transcriptionnel et du métabolisme des cellules cancéreuses présentant la mutation oncogène KRAS G13D

Résumé en anglais

Background : Activating mutations in KRAS frequently occur in colorectal cancer (CRC) patients, leading to resistance to EGFR-targeted therapies.

Methods : To better understand the cellular reprogramming which occurs in mutant KRAS cells, we have undertaken a systems-level analysis of four CRC cell lines which express either wild type (wt) KRAS or the oncogenic KRASG13D allele (mtKRAS).

Results : RNAseq revealed that genes involved in ribosome biogenesis, mRNA translation and metabolism were significantly upregulated in mtKRAS cells. Consistent with the transcriptional data, protein synthesis and cell proliferation were significantly higher in the mtKRAS cells. Targeted metabolomics analysis also confirmed the metabolic reprogramming in mtKRAS cells. Interestingly, mtKRAS cells were highly transcriptionally responsive to EGFR activation by TGF