Sun Naihui, Zhao Xing
Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Pediatrics, The First Affiliated Hospital of China Medical University, Shenyang, China.
Front Pharmacol. 2022 Jul 15;13:935553. doi: 10.3389/fphar.2022.935553. eCollection 2022.
Metabolic reprogramming is an emerging hallmark of tumor cells. In order to survive in the nutrient-deprived environment, tumor cells rewire their metabolic phenotype to provide sufficient energy and build biomass to sustain their transformed state and promote malignant behaviors. Amino acids are the main compositions of protein, which provide key intermediate substrates for the activation of signaling pathways. Considering that cells can synthesize arginine argininosuccinate synthase 1 (ASS1), arginine is regarded as a non-essential amino acid, making arginine depletion as a promising therapeutic strategy for ASS1-silencing tumors. In this review, we summarize the current knowledge of expression pattern of ASS1 and related signaling pathways in cancer and its potential role as a novel therapeutic target in cancer. Besides, we outline how ASS1 affects metabolic regulation and tumor progression and further discuss the role of ASS1 in arginine deprivation therapy. Finally, we review approaches to target ASS1 for cancer therapies.
代谢重编程是肿瘤细胞新出现的一个特征。为了在营养匮乏的环境中存活,肿瘤细胞会重塑其代谢表型,以提供足够的能量并构建生物量,从而维持其转化状态并促进恶性行为。氨基酸是蛋白质的主要组成部分,为信号通路的激活提供关键的中间底物。鉴于细胞可以合成精氨酸(精氨酸琥珀酸合成酶1,ASS1),精氨酸被视为非必需氨基酸,这使得精氨酸剥夺成为一种针对ASS1沉默型肿瘤的有前景的治疗策略。在本综述中,我们总结了目前关于ASS1在癌症中的表达模式、相关信号通路及其作为癌症新型治疗靶点的潜在作用的知识。此外,我们概述了ASS1如何影响代谢调节和肿瘤进展,并进一步讨论了ASS1在精氨酸剥夺治疗中的作用。最后,我们综述了针对癌症治疗靶向ASS1的方法。