Stromal Hedgehog signalling is downregulated in colon cancer and its restoration restrains tumour growth

Related Experiment Video

Updated: Mar 16, 2026

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
07:26

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

Published on: January 31, 2025

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Marco Gerling1, Nikè V J A Büller2, Leonard M Kirn1,3

  • 1Center for Innovative Medicine, Department of Biosciences and Nutrition, Karolinska Institutet, NOVUM, Hälsovägen 7, 14183 Huddinge, Sweden.

Nature Communications
|August 6, 2016
PubMed

Insights

Diminished Hedgehog (Hh) signalling promotes colorectal cancer (CRC) development. Activating stromal Hh signalling unexpectedly suppresses colon tumors, suggesting a novel therapeutic strategy for CRC.

Area of Science:

  • Oncology
  • Developmental Biology
  • Cancer Signalling

Background:

  • Hedgehog (Hh) signalling is implicated in colorectal cancer (CRC) development, with upregulated Hh ligands observed in many solid tumors.
  • However, clinical trials using Hh antagonists have yielded no benefit, suggesting a complex role for Hh in CRC.

Purpose of the Study:

  • To investigate the role of downstream Hh signalling activity in a mouse model of colitis-associated colon cancer.
  • To determine the therapeutic potential of modulating Hh signaling in colorectal cancer.

Main Methods:

  • Utilized Hh reporter mice to assess downstream Hh activity in a colitis-associated colon cancer model.
  • Investigated the effects of stroma-specific Hh activation and attenuated Hh signalling on tumor progression.
  • Analyzed downstream Hh activity in human CRC samples.

Main Results:

  • Downstream Hh activity was unexpectedly diminished and restricted to the stroma in a mouse model of colon cancer.
  • Stroma-specific Hh activation significantly reduced tumor load and blocked advanced neoplasm progression in mice.
  • Attenuated Hh signalling accelerated colonic tumorigenesis, while human CRC showed similarly reduced downstream Hh activity.

Conclusions:

  • Diminished downstream Hh signalling enhances colorectal cancer development.
  • Stromal Hh activation acts as a colon tumor suppressor, potentially through modulation of BMP signalling and colonic stem cell signatures.
  • Targeting stromal Hh signalling represents a potential therapeutic strategy for colorectal cancer.

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