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Multi-Omics Insights into the Impact of MDH2 on Breast Cancer Progression: A Promising Druggable Target

Botao Pan1, Zirun Luo2, Xiujuan Yang1

  • 1Scientific Research Center, The Affiliated Foshan Women and Children Hospital, Guangdong Medical University, Foshan, 528000, China.

Oncology Research
|November 3, 2025
PubMed
Abstract

Insights

Malate dehydrogenase 2 (MDH2) drives breast cancer growth by altering cell metabolism and promoting metastasis. Targeting MDH2 offers a promising therapeutic strategy for breast cancer treatment.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • Breast cancer exhibits significant metabolic dysregulation, with altered enzyme activity playing a key role.
  • Malate dehydrogenase 2 (MDH2), a tricarboxylic acid cycle enzyme, is implicated in malignancies, but its specific role in breast cancer is unclear.

Purpose of the Study:

  • To elucidate the oncogenic role of MDH2 in breast cancer.
  • To evaluate MDH2 as a diagnostic, therapeutic, and prognostic biomarker for breast cancer.

Main Methods:

  • Combined in vitro cell-based assays and mouse xenograft models.
  • Assessed effects of MDH2 expression on proliferation, migration, epithelial-mesenchymal transition (EMT), glucose consumption, and ATP production.
  • Utilized transcriptomic profiling, metabolomics, and in silico druggability analyses.

Main Results:

  • MDH2 depletion suppressed breast cancer cell proliferation, migration, and reversed EMT, while reducing glucose consumption and ATP production.
  • MDH2 overexpression accelerated xenograft tumor growth and affected metastasis-related gene expression.
  • Identified the PI3K/AKT pathway as a downstream effector and confirmed MDH2 as a druggable target.

Conclusions:

  • MDH2 plays a significant role in breast cancer metabolism and progression.
  • MDH2 is a promising therapeutic target for breast cancer treatments focused on metabolism and tumor growth.
Keywords:
Breast cancercancer metabolismdruggable targetimmunomodulatory metabolitesmalate dehydrogenase 2 (MDH2)

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