Rethinking glutamine metabolism and the regulation of glutamine addiction by oncogenes in cancer

作者全名："Ni, Rui; Li, Ziwei; Li, Li; Peng, Dan; Ming, Yue; Li, Lin; Liu, Yao"

作者地址："[Ni, Rui; Li, Ziwei; Li, Li; Peng, Dan; Ming, Yue; Liu, Yao] Army Med Univ, Daping Hosp, Dept Pharm, Chongqing, Peoples R China; [Li, Lin] Chongqing Med Univ, Chongqing Hlth Ctr Women & Children, Dept Pharm, Women & Childrens Hosp, Chongqing, Peoples R China"

通信作者："Liu, Y (通讯作者)，Army Med Univ, Daping Hosp, Dept Pharm, Chongqing, Peoples R China.; Li, L (通讯作者)，Chongqing Med Univ, Chongqing Hlth Ctr Women & Children, Dept Pharm, Women & Childrens Hosp, Chongqing, Peoples R China."

来源：FRONTIERS IN ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000950952200001

JCR分区：Q2

影响因子：3.5

年份：2023

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Review

关键词：glutamine metabolism; oncogene; glutamine addiction; metabolism inhibiton; cancer therapy

摘要："Glutamine, the most abundant non-essential amino acid in human blood, is crucial for cancer cell growth and cancer progression. Glutamine mainly functions as a carbon and nitrogen source for biosynthesis, energy metabolism, and redox homeostasis maintenance in cancer cells. Dysregulated glutamine metabolism is a notable metabolic characteristic of cancer cells. Some carcinogen-driven cancers exhibit a marked dependence on glutamine, also known as glutamine addiction, which has rendered the glutamine metabolic pathway a breakpoint in cancer therapeutics. However, some cancer cells can adapt to the glutamine unavailability by reprogramming metabolism, thus limiting the success of this therapeutic approach. Given the complexity of metabolic networks and the limited impact of inhibiting glutamine metabolism alone, the combination of glutamine metabolism inhibition and other therapeutic methods may outperform corresponding monotherapies in the treatment of cancers. This review summarizes the uptake, transport, and metabolic characteristics of glutamine, as well as the regulation of glutamine dependence by some important oncogenes in various cancers to emphasize the therapeutic potential of targeting glutamine metabolism. Furthermore, we discuss a glutamine metabolic pathway, the glutaminase II pathway, that has been substantially overlooked. Finally, we discuss the applicability of polytherapeutic strategies targeting glutamine metabolism to provide a new perspective on cancer therapeutics."

基金机构：Chongqing Special Project for Technological Innovation and Application Development [CSTC2021jscx-gksb-N0013]; Chongqing Traditional Chinese Medicine Research Project [2023ZDXM032]

基金资助正文：Funding This work was financially supported by The Chongqing Special Project for Technological Innovation and Application Development (NO. CSTC2021jscx-gksb-N0013) and The Chongqing Traditional Chinese Medicine Research Project (NO. 2023ZDXM032).