Transcriptional and metabolic rewiring of colorectal cancer cells expressing the oncogenic KRAS^G13D mutation.

ABSTRACT:

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 KRAS^G13D 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. Interestingl

SUBMITTER: Charitou T 

PROVIDER: S-EPMC6738113 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature