Related Experiment Video

Updated: Sep 12, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

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Baseline expression of c-Myc defines the tissue specificity of oncogenic K-Ras

Olesja Popow, Qing Yu, Clarance Yapp

    Biorxiv : the Preprint Server for Biology
    |August 8, 2025
    PubMed

    Insights

    Oncogenic KRAS mutations are frequent in cancer but tissue-specific. Low c-Myc levels prevent activated K-Ras from affecting cell fitness, revealing a key mechanism for oncogene tissue specificity.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Genetics

    Background:

    • KRAS is a frequently mutated oncogene in cancer.
    • KRAS mutations exhibit tissue-specific prevalence, necessitating investigation into underlying mechanisms.
    • Understanding oncogene tissue specificity is crucial for targeted cancer therapies.

    Purpose of the Study:

    • To investigate the molecular mechanisms of KRAS oncogene tissue specificity.
    • To determine factors influencing the cellular response to activated K-Ras.
    • To identify potential therapeutic targets for KRAS-driven cancers.

    Main Methods:

    • Utilized genetically engineered mouse models with a conditional oncogenic Kras allele.
    • Expressed activated K-Ras (K-Ras G12D) in adult mouse tissues.
    • Assessed the impact of K-Ras G12D on cell fitness and signaling pathways, including c-Myc and MAPK.

    Main Results:

    • Activated K-Ras (K-Ras G12D) cell fitness effects are independent of canonical MAPK signaling.
    • Low baseline c-Myc expression renders tissues non-permissive to oncogenic K-Ras.
    • Ectopic c-Myc expression in the liver reversed the non-permissive state.
    • Tissue permissiveness to oncogenic K-Ras is independent of proliferation rate, cell cycle arrest, or apoptosis.

    Conclusions:

    • Basal c-Myc levels are critical determinants of oncogene specificity for KRAS.
    • Tissue-inherent signaling networks, particularly c-Myc expression, dictate responses to oncogenic KRAS.
    • These findings offer insights into targeted cancer therapy development for KRAS-mutated tumors.

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