The role of glutaminase in cancer

Abstract

Increased glutamine metabolism (glutaminolysis) is a hallmark of cancer and is recognised as a key metabolic change in cancer cells. Breast cancer is a heterogeneous disease with different morphological and molecular subtypes and responses to therapy, and breast cancer cells are known to rewire glutamine metabolism to support survival and proliferation. Glutaminase isoenzymes (GLS and GLS2) are key enzymes for glutamine metabolism. Interestingly, GLS and GLS2 have contrasting functions in tumorigenesis. In this review, we explore the role of glutaminase in cancer, primarily focusing on breast cancer, address the role played by oncogenes and tumour suppressor genes in regulating glutaminase, and discuss current therapeutic approaches to targeting glutaminase.

TMEM180 contributes to colorectal cancer proliferation through intracellular metabolic pathways

“…(liver-type) (20). Elevated expression of GLS has been observed in several types of cancer (21). In CRC, high expression of GLS is correlated with poor prognosis (22).…”

Identified metabolic related genes to construct a prognostic model of Breast cancer patients

“…Glycolysis in BC tissues and BC cell lines is more active than paracancerous and normal breast epithelial cell lines [24,25]. Amino acid metabolism, especially glutamine metabolism, is closely related to breast cancer development [10]. There are two key enzymes in the glutamine metabolism of tumors, GLS and GLS-2 [11].…”

“…The Warburg effect is found in a variety of solid tumors including BC [9]. In addition, the role of glutamine metabolic pathways in tumors should not be underestimated [10]. There are two subtypes of glutaminase (GLS), kidney-type (GLS) and liver-type (GLS2), which play opposite roles in tumor development [11][12][13].…”

Crosstalks of GSK3 signaling with the mTOR network and effects on targeted therapy of cancer

“…Glutaminase (GLS) is the enzyme that catalyzes the lysis of glutamine to glutamate. Two isoforms of GLS exist, GLS1 and GLS2 [125]. Importantly, evidence shows that glutaminolysis is associated with the enhanced activity of c-Myc [126], a target of GSK3 signaling.…”