MCT4

Alterations in metabolic activity contribute to the proliferation and survival of cancer cells and most display an increase in glucose usage and lactate secretion even in the presence of oxygen. This feature is known as aerobic glycolysis or Warburg Effect.

Through the integration of whole-genome siRNA screening, mRNA expression analysis and metabolic assays, PREDICT has identified the monocarboxylate transporter MCT4 as a key mediator of the Warburg effect in renal cell carcinoma.

Inhibition of this lactate transporter resulted in intracellular acidosis, reduction in intracellular ATP production and cell death. Notably, high expression of MCT4 correlated with shorter relapse free survival periods in renal cell carcinoma patients and was higher at sites of metastatic disease.

The data obtained by PREDICT suggest that MCT4 is a potential new drug target in renal cell carcinoma.

Figure: A genome-wide siRNA screen identify 297 essential genes in renal cell carcinoma cells. 14 of these genes are overexpressed in tumour samples compared to normal kidney tissue, including MCT4.

siRNA ranking

Reference:

http://www.ncbi.nlm.nih.gov/pubmed/22362593

Gerlinger M, Santos CR, Spencer-Dene B, Martinez P, Endesfelder D, Burrell RA, Vetter M, Jiang M, Saunders RE, Kelly G, Dykema K, Rioux-Leclercq N, Stamp G, Patard JJ, Larkin J, Howell M,Swanton C. Genome-wide RNA interference analysis of renal carcinoma survival regulators identifies MCT4 as a Warburg effect metabolic target. J Pathol. 2012 Jun;227(2):146-56. doi: 10.1002/path.4006. Epub 2012 Apr 18. PMID: 22362593

Leave a Comment

No Comments Yet!