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7-amino carboxycoumarin 2 inhibits lactate induced epithelial-to-mesenchymal transition via MPC1 in oral and breast

Sheikh Mohammad Umar1, Arundhathi J R Dev1, Akanksha Kashyap1

  • 1Department of Medical Oncology (Lab), All India Institute of Medical Sciences, New Delhi, India.

Cell Biology International
|May 22, 2024
PubMed
Summary
This summary is machine-generated.

Extracellular lactate fuels oral and breast cancer aggressiveness by promoting oxidative phosphorylation. Inhibiting lactate transport via MPC inhibitor 7ACC2 shows therapeutic potential against these malignant oxidative cancers.

Keywords:
7ACC2AZD3965MPC1OXPHOSepithelial to mesenchymal transition (EMT)lactate

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Area of Science:

  • Oncology
  • Cancer Metabolism
  • Molecular Biology

Background:

  • Lactate acts as an oncometabolite, influencing tumor aggressiveness.
  • Cancer cells utilize lactate from the tumor microenvironment (TME) for energy via mitochondrial oxidative phosphorylation (OXPHOS).

Purpose of the Study:

  • To investigate the role of lactate in oral squamous cell carcinoma (OSCC) and breast cancer.
  • To evaluate the therapeutic potential of targeting lactate metabolism in these cancers.

Main Methods:

  • Meta-analysis of gene expression in OSCC and breast cancer.
  • Experimental treatment of OSCC (SCC4) and breast cancer (MDA-MB-231) cells with L-lactate.
  • Assessment of epithelial-mesenchymal transition (EMT) and cell migration.
  • Inhibition of lactate transporters using AZD3965 (MCT1 inhibitor) and 7ACC2 (MPC inhibitor).

Main Results:

  • Overexpression of glycolytic and OXPHOS genes was observed in OSCC, similar to breast cancer.
  • L-lactate treatment induced EMT and migration in cancer cells.
  • The MPC inhibitor 7ACC2 effectively neutralized L-lactate-induced EMT and migration, while the MCT1 inhibitor AZD3965 did not.
  • Lactate treatment increased MPC1 expression, potentially enhancing sensitivity to 7ACC2.

Conclusions:

  • Extracellular lactate positively regulates MPC1 expression in cancer cells.
  • Targeting lactate import via MPC inhibition (e.g., with 7ACC2) is a promising therapeutic strategy for malignant oxidative cancers.
  • Further preclinical studies are needed to validate these findings.