A systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions

Priti Chatterjee1, Debaleena Bhowmik1,2, Sib Sankar Roy1,2

  • 1Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.

Channels (Austin, Tex.)
|November 7, 2023
PubMed

Insights

Monocarboxylate transporters (MCTs) are vital in ovarian cancer. MCT4 is linked to poor survival and cancer cell invasion, making it a potential therapeutic target.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • Monocarboxylate transporters (MCTs), encoded by the SLC16A gene family, regulate pyruvate and lactate transport.
  • MCTs are crucial for cellular metabolism, particularly in solid tumors.
  • Their role in oncogenesis highlights the need to study their association with Epithelial ovarian cancer (EOC).

Purpose of the Study:

  • To investigate the association of MCT1, MCT2, MCT3, and MCT4 with Epithelial ovarian cancer (EOC) pathophysiology.
  • To evaluate MCT4 as a prognostic marker and therapeutic target in EOC.
  • To compare the efficacy of different MCT inhibitors on EOC cell invasion.

Main Methods:

  • Utilized publicly available databases and web resources for in silico analysis.
  • Performed in vitro experiments in EOC cell lines (SKOV3, OAW-42).
  • Analyzed mRNA expression levels and patient survival data.
  • Compared the effects of MCT blockers SR13800 and α-Cyano Hydroxy Cinnamic Acid (α-CHCA).

Main Results:

  • MCT1 and MCT4 mRNA were upregulated in ovarian cancer tissues compared to normal tissues.
  • Elevated MCT4 mRNA levels correlated with poorer patient survival.
  • MCT4 showed positive correlation with gene families involved in invasion, migration, and immune modulation.
  • The broad-spectrum MCT blocker α-CHCA demonstrated a greater reduction in cancer cell invasion than the MCT1/2 blocker SR13800.

Conclusions:

  • MCT4 is a significant factor in EOC pathophysiology, associated with aggressive tumor behavior.
  • MCT4 serves as a potential prognostic marker for predicting poor patient outcomes in EOC.
  • MCT4 represents a promising therapeutic target for EOC intervention.