Oncogenic KRAS represses the dependence receptor UNC5C via ERK2-FOS signaling in non-small cell lung cancer

Related Experiment Video

Updated: Jun 21, 2026

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

Deyu Wang1, Man Xiao2, Kaicheng Zhou3

  • 1Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, P.R. China.

The Journal of Biological Chemistry
|June 19, 2026
PubMed

Insights

Oncogenic KRAS signaling suppresses the tumor suppressor UNC5C in non-small cell lung cancer (NSCLC). This study reveals the RAF/MEK/ERK pathway, specifically ERK2 and FOS, mediates this KRAS-driven UNC5C downregulation.

Area of Science:

  • Molecular Oncology
  • Cancer Biology
  • Cell Signaling

Background:

  • KRAS mutations are common drivers in non-small cell lung cancer (NSCLC).
  • UNC5C acts as a tumor suppressor by inducing apoptosis, but its downregulation mechanism in cancer is unclear.
  • Understanding UNC5C regulation is crucial for developing targeted therapies.

Purpose of the Study:

  • To elucidate the mechanism by which oncogenic KRAS signaling affects UNC5C expression in NSCLC.
  • To identify the specific signaling pathways involved in KRAS-mediated UNC5C suppression.
  • To investigate the role of UNC5C as a tumor suppressor in KRAS-mutant NSCLC.

Main Methods:

  • Investigated UNC5C expression in KRAS-mutant NSCLC cell lines.
  • Utilized pathway inhibitors (RAF/MEK/ERK, PI3K/AKT/mTOR) to assess signaling impacts.
  • Performed molecular analyses to identify transcription factors regulating UNC5C.
  • Compared UNC5C downregulation levels across different NSCLC subtypes.

Main Results:

  • Oncogenic KRAS was found to suppress UNC5C expression in KRAS-mutant NSCLC.
  • The RAF/MEK/ERK pathway, particularly ERK2, mediated KRAS-driven UNC5C downregulation.
  • FOS, a downstream transcription factor of ERK, was identified as the repressor of UNC5C transcription.
  • UNC5C showed significant downregulation in NSCLC and exhibited tumor suppressor activity.

Conclusions:

  • Oncogenic KRAS transcriptionally suppresses UNC5C in NSCLC via the ERK2/FOS pathway.
  • This study deciphers a key molecular mechanism in KRAS-driven lung cancer.
  • UNC5C represents a potential therapeutic target in KRAS-mutant NSCLC.
Keywords:
KRASNSCLCUNC5Cdependence receptorstumor suppressor genes

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