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Targeting GLS1 to cancer therapy through glutamine metabolism

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Abstract

Glutamine metabolism is one of the hallmarks of cancers which is described as an essential role in serving as a major energy and building blocks supply to cell proliferation in cancer cells. Many malignant tumor cells always display glutamine addiction. The “kidney-type” glutaminase (GLS1) is a metabolism enzyme which plays a significant part in glutaminolysis. Interestingly, GLS1 is often overexpressed in highly proliferative cancer cells to fulfill enhanced glutamine demand. So far, GLS1 has been proved to be a significant target during the carcinogenesis process, and emerging evidence reveals that its inhibitors could provide a benefit strategy for cancer therapy. Herein, we summarize the prognostic value of GLS1 in multiple cancer type and its related regulatory factors which are associated with antitumor activity. Moreover, this review article highlights the remarkable reform of discovery and development for GLS1 inhibitors. On the basis of case studies, our perspectives for targeting GLS1 and development of GLS1 antagonist are discussed in the final part.

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Data availability statement

The raw date supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher.

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Funding

This study is supported by the National Key Research and Development Program of China (Grant No. 2017YFA0205200), the National Natural Science Foundation of China (Grant Nos. 81771957, 81801811).

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Author notes

  1. Wei Yu and XiangYu Yang contributed equally to this work.

Authors and Affiliations

  1. China Pharmaceutical University, Nanjing, 21000, Jiangsu, China

    Wei Yu, Qian Zhang, Li Sun & ShengTao Yuan

  2. Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People’s Hospital, Zhuhai Hospital Affiliated With Jinan University, Jinan University, Zhuhai, 519000, Guangdong, China

    Wei Yu, XiangYu Yang & YongJie Xin

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  1. Wei Yu
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Yu, W., Yang, X., Zhang, Q. et al. Targeting GLS1 to cancer therapy through glutamine metabolism. Clin Transl Oncol 23, 2253–2268 (2021). https://doi.org/10.1007/s12094-021-02645-2

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