Arginine signaling and cancer metabolism

Chia Lin Chen, Sheng Chieh Hsu, David K. Ann, Yun Yen, Hsing Jien Kung

研究成果: 雜誌貢獻回顧型文獻同行評審

1 引文 斯高帕斯(Scopus)

摘要

Arginine is an amino acid critically involved in multiple cellular processes including the syntheses of nitric oxide and polyamines, and is a direct activator of mTOR, a nutrient-sensing kinase strongly implicated in carcinogenesis. Yet, it is also considered as a non-or semi-essential amino acid, due to normal cells’ intrinsic ability to synthesize arginine from citrulline and aspartate via ASS1 (argininosuccinate synthase 1) and ASL (argininosuccinate lyase). As such, arginine can be used as a dietary supplement and its depletion as a therapeutic strategy. Strikingly, in over 70% of tumors, ASS1 transcription is suppressed, rendering the cells addicted to external arginine, forming the basis of arginine-deprivation therapy. In this review, we will discuss arginine as a signaling metabolite, arginine’s role in cancer metabolism, arginine as an epigenetic regulator, arginine as an immunomodulator, and arginine as a therapeutic target. We will also provide a comprehensive summary of ADI (arginine deiminase)-based arginine-deprivation preclinical studies and an update of clinical trials for ADI and arginase. The different cell killing mechanisms associated with various cancer types will also be described.
原文英語
文章編號3541
期刊Cancers
13
發行號14
DOIs
出版狀態已發佈 - 七月 2021

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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