English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

KRAS  was one of the earliest human oncogenes to be described and is one of the most commonly mutated genes in different human cancers, including colorectal cancer. Despite  KRAS  mutants being known driver mutations,  KRAS  has proved difficult to target therapeutically, necessitating a comprehensive understanding of the molecular mechanisms underlying  KRAS -driven cellular transformation.    Objectives  To investigate the metabolic signatures associated with single copy mutant  KRAS  in isogenic human colorectal cancer cells and to determine what metabolic pathways are affected.    Methods  Using NMR-based metabonomics, we compared wildtype (WT)- KRAS  and mutant  KRAS  effects on cancer cell metabolism using metabolic profiling of the parental  KRAS   G13D/+  HCT116 cell line and its isogenic, derivative cell lines  KRAS   +/–  and  KRAS   G13D/– .    Results  Mutation in the  KRAS  oncogene leads to a general metabolic remodelling to sustain growth and counter stress, including alterations in the metabolism of amino acids and enhanced glutathione biosynthesis. Additionally, we show that  KRAS   G13D/ +  and  KRAS   G13D/−   cells have a distinct metabolic profile characterized by dysregulation of TCA cycle, up-regulation of glycolysis and glutathione metabolism pathway as well as increased glutamine uptake and acetate utilization.    Conclusions  Our study showed the effect of a single point mutation in one  KRAS  allele and  KRAS  allele loss in an isogenic genetic background, hence avoiding confounding genetic factors. Metabolic differences among different  KRAS  mutations might play a role in their different responses to anticancer treatments and hence could be exploited as novel metabolic vulnerabilities to develop more effective therapies against oncogenic  KRAS.Graphical abstractSupplementary Information  The online version contains supplementary material available at 10.1007/s11306-021-01852-w.

Metabonomics study of the effects of single copy mutant KRAS in the presence or absence of WT allele using human HCT116 isogenic cell lines