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Functional screening identifies MCT4 as a key regulator of breast cancer cell metabolism and survival

Franziska Baenke1, Sébastien Dubuis2, Charlene Brault3

  • 1Gene Expression Analysis Laboratory, Cancer Research UK London Research Institute, UK.

The Journal of Pathology
|May 13, 2015
PubMed

Insights

Monocarboxylate transporter 4 (MCT4) is crucial for breast cancer cell survival by regulating pH and metabolism. Its inhibition increases cancer cell reliance on respiration and glutamine, suggesting MCT4 as a therapeutic target.

Area of Science:

  • Oncology
  • Cancer Metabolism
  • Molecular Biology

Background:

  • Cancer cells exhibit metabolic reprogramming to support biosynthesis and survival.
  • Oncogenic drivers alter metabolic pathways, creating vulnerabilities in cancer cells.
  • Understanding metabolic dependencies is key to developing targeted cancer therapies.

Purpose of the Study:

  • To identify selective metabolic dependencies in breast cancer.
  • To investigate the role of monocarboxylate transporter 4 (MCT4) in breast cancer cell survival and metabolism.

Main Methods:

  • Functional screening of 17 diverse breast cancer cell lines.
  • Depletion of MCT4 to assess its impact on cell metabolism and survival.
  • Analysis of MCT4 regulation by the PI3K-Akt signaling pathway.

Main Results:

  • Monocarboxylate transporter 4 (MCT4) is a critical regulator of breast cancer cell survival.
  • MCT4 supports pH homeostasis, lactate secretion, and non-oxidative glucose metabolism.
  • MCT4 depletion enhances cancer cell dependence on mitochondrial respiration and glutamine metabolism, impairing 3D growth.
  • MCT4 expression is linked to the PI3K-Akt pathway and is elevated in HER2-positive breast cancers.

Conclusions:

  • MCT4 is a potential therapeutic target for specific breast cancer subtypes.
  • Targeting MCT4 may offer novel combination treatment strategies for breast cancer.
Keywords:
HER2MCT4PI3K-Akt pathwaybreast cancerlactatemetabolism

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