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Updated: Jan 15, 2026

In vitro Organoid Culture of Primary Mouse Colon Tumors
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In vitro Organoid Culture of Primary Mouse Colon Tumors

Published on: May 17, 2013

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STAG2 mutations in the normal colon induce upregulation of oncogenic pathways in neighbouring wildtype cells

Wei Ni Yew1, Christopher James Dean2, Dedrick Kok Hong Chan1,3,4

  • 1Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Plos One
|October 15, 2025
PubMed

Insights

STAG2 mutations in normal colon cells can promote colorectal cancer by influencing nearby healthy cells. This study reveals a novel cell-interactive mechanism driving oncogenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Driver mutations in normal colon cells are implicated in colorectal cancer.
  • The precise role and function of these mutations in oncogenesis require further elucidation.

Purpose of the Study:

  • To investigate the role of STAG2 mutants in the normal colon.
  • To determine the transcriptional impact of STAG2 mutations on wildtype colon organoids.

Main Methods:

  • Utilized patient-derived wildtype colon organoids.
  • Employed CRISPR-Cas9 gene editing to generate STAG2 mutants.
  • Performed co-culture experiments and single-cell RNA sequencing (scRNAseq) to analyze transcriptional changes.

Main Results:

  • Wildtype organoids co-cultured with STAG2 mutants showed upregulation of oncogenic pathways.
  • Specifically, TNFα-signaling and KRAS-signaling pathways were activated in wildtype organoids.
  • STAG2 mutant cells demonstrated a pro-oncogenic effect through cell-cell interaction, not cell-autonomous action.

Conclusions:

  • STAG2 mutant cells can promote colorectal oncogenesis via paracrine signaling to neighboring wildtype cells.
  • This study identifies a novel mechanism of colorectal cancer development involving intercellular communication.
  • Findings suggest STAG2 mutations play a critical role in early-stage colorectal tumorigenesis.

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