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Targeting plasma membrane cholesterol as a novel anticancer therapy

Alfredo Erazo-Oliveras1, Mónica Muñoz-Vega1, Robert S Chapkin1

  • 1Program in Integrative Nutrition & Complex Diseases, Texas A&M University, College Station, TX 77843, USA; Department of Nutrition, Texas A&M University, College Station, TX 77843, USA; Texas A&M Regional Center of Excellence in Cancer Research, Texas A&M University, College Station, TX 77843, USA.

Trends in Pharmacological Sciences
|June 20, 2025
PubMed

Insights

Researchers identified a new way to target colon cancer by blocking a pathway involving cholesterol and a protein called Dvl. This offers a potential new therapeutic strategy for treating oncogenic Wnt signaling in colorectal cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Targeting oncogenic Wnt signaling in colorectal cancer (CRC) is a significant challenge.
  • The canonical adenomatous polyposis coli (APC) pathway plays a crucial role in CRC development.
  • Effective therapeutic strategies for CRC remain limited.

Purpose of the Study:

  • To elucidate a novel mechanistic link between APC loss, membrane cholesterol, and Wnt signaling in CRC.
  • To identify an innovative drug target for suppressing the cholesterol-Dvl-β-catenin signaling axis.
  • To develop a targeted therapeutic strategy for colorectal cancer.

Main Methods:

  • Investigated the role of membrane cholesterol in Wnt pathway activation.
  • Analyzed the interaction between Dvl protein and cholesterol in CRC cells.
  • Developed and tested a novel drug targeting the cholesterol-Dvl-β-catenin axis.

Main Results:

  • Demonstrated a direct mechanistic link between loss of APC function and altered membrane cholesterol levels.
  • Showed that cholesterol accumulation promotes the Dvl-β-catenin signaling axis.
  • Identified a novel drug target that specifically suppresses this axis.

Conclusions:

  • Loss of APC function in colorectal cancer is associated with altered membrane cholesterol.
  • The cholesterol-Dvl-β-catenin axis represents a novel therapeutic target for CRC.
  • This study provides a promising new strategy for treating oncogenic Wnt signaling-driven colorectal cancer.
Keywords:
DvlWntcholesterolcolon cancerplasma membranetherapeutics

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