Glutaminase sustains cell survival via the regulation of glycolysis and glutaminolysis in colorectal cancer.

Cancer cells remodel their metabolic programs towards aerobic glycolysis and elevated glutaminolysis to meet the requirement s of rapid proliferation. Understanding how cells sense and adapt to these changes may provide new targets for therapeutic intervention. Deamination of glutamine to glutamate by glutaminase (GLS1) is an essential step in glutaminolysis. The present study revealed that the loss of GLS1 expression by RNA interference or inhibitor decreased the proliferation and viability of colorectal cancer (CRC) cells. The abrogation of GLS1 function notably inhibited glutaminolysis and aerobic glycolysis, which resulted in the decrease of internal ATP levels and an increase in cell death. In addition, GLS1 expression was significantly elevated in CRC tissues in comparison with adjacent normal tissues (P<0.001), which is associated with the cell differentiation status and tumor node metastasis stage. In conclusion, the present study defined a key role of GLS1 in coupling glutaminolysis with elevated glucose uptake and consequently the growth of colon cancer cells. Due to the functional importance of GLS1 in regulating cell metabolism, it was proposed that GLS1 may serve as a target for colorectal cancer therapy.