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Related Experiment Video

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β-Catenin-Facilitated Glycolytic Reprogramming Fuels TNBC Progression: Therapeutic Blockade with XAV939.

Sheikh Mohammad Umar1, Shruti Kahol2, Sandeep R Mathur2

  • 1Department of Medical Oncology (Lab), Dr BRA IRCH, AIIMS, Ansari Nagar, New Delhi, India.

Technology in Cancer Research & Treatment
|February 17, 2026
PubMed
Summary

Beta-catenin drives aerobic glycolysis and metastasis in Triple-Negative Breast Cancers (TNBCs). Inhibiting beta-catenin with XAV939 suppressed TNBC progression and shows therapeutic potential.

Keywords:
XAV939aerobic glycolysismigrationtriple negative breast cancerβ-catenin

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The glycolytic phenotype promotes cancer cell migration and metastasis, particularly in Triple-Negative Breast Cancers (TNBCs).
  • Understanding the molecular pathways driving aerobic glycolysis in TNBCs is crucial for identifying progression drivers.

Purpose of the Study:

  • To investigate the role of beta-catenin in regulating aerobic glycolysis in TNBCs.
  • To evaluate the therapeutic potential of the beta-catenin inhibitor XAV939 in TNBC models.

Main Methods:

  • Immunohistochemistry (IHC) assessed beta-catenin and glycolytic proteins (PFKP, LDHA, MCT1) in 98 TNBC patients.
  • Kaplan-Meier and Cox regression analyzed prognostic value.
  • In vitro studies used XAV939 with MTT, Western blotting, wound healing, invasion, and colony formation assays.

Main Results:

  • Beta-catenin and glycolytic markers were overexpressed in over 50% of TNBCs.
  • Combined expression correlated with reduced patient survival.
  • XAV939 suppressed beta-catenin, glycolytic proteins, and aerobic glycolysis, impairing TNBC cell proliferation, migration, invasion, and clonogenicity.

Conclusions:

  • Beta-catenin critically controls aerobic glycolysis by regulating key glycolytic proteins, driving TNBC progression and metastasis.
  • XAV939 effectively inhibits the glycolytic phenotype, indicating its therapeutic promise for TNBC treatment.