title: Elevated expression of glutaminase confers glucose utilization via glutaminolysis in prostate cancer.
abstract: Cancer cells reprogram their metabolism towards aerobic glycolysis and elevated glutaminolysis, which contributes to the aggressive phenotype. Understanding how these metabolic pathways are regulated may provide critical targets for therapeutic intervention. Glutaminase (GLS1) is a key enzyme that converts glutamine to glutamate. In this study, we show the loss of GLS1 function by RNA interference or inhibitor diminished the rates of glucose utilization, growth and invasiveness of prostate cancer cells. We propose that GLS1 positively regulates glucose uptake in addition to glutaminolysis. Further, GLS1 involves the transcriptional repression of thioredoxin interacting protein (TXNIP), which is a potent negative regulator of glucose uptake and aerobic glycolysis. Most importantly, we provided direct evidence that elevated GLS1 expression was highly correlated with the tumor stage and progression in prostate cancer patients. Together, we defined a key role for GLS1 in coupling glutaminolysis of the TCA cycle with elevated glucose uptake and consequently the growth of prostate cancer cells. These data extends the role of GLS1 in regulating cell metabolism and the clinical utility of GLS1 inhibitors in the restriction of essential nutrients.
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, Hubei, China.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Pan
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, Hubei, China. Electronic address: biogaolei@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, Hubei, China.
authors.forename: Guoqiu
authors.initials: G
authors.lastname: Shen
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, Hubei, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Xie
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, Hubei, China.
authors.forename: Handong
authors.initials: H
authors.lastname: Wen
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, Hubei, China.
authors.forename: Jiarong
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, Hubei, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, Hubei, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Department of Urology, Wuhan General Hospital of Guangzhou Military Region, Wuhan, Hubei, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Qian
mesh_terms: D000255:Adenosine Triphosphate; D002352:Carrier Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005972:Glutaminase / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009361:Neoplasm Invasiveness; D011467:Prostate / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology*; D034622:RNA Interference
chemical_list: D002352:Carrier Proteins; C486715:TXNIP protein, human; D005973:Glutamine; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; C579480:GLS protein, human; D005972:Glutaminase; D005947:Glucose
keywords: GLS1; GLUT1; Glucose; Glutamine; Prostate cancer; TXNIP