Amino acid sensing in cancer

Zihao Lin; Lihong He; Jiawei Wang; Hanjia Zhang; Shicheng Yao; Jingpeng Guo; Xiaozhen Zhang; Tingbo Liang; Xueli Bai

doi:10.1016/j.phrs.2025.108003

Amino acid sensing in cancer

Pharmacol Res. 2025 Nov:221:108003. doi: 10.1016/j.phrs.2025.108003. Epub 2025 Oct 19.

Authors

Zihao Lin¹, Lihong He¹, Jiawei Wang¹, Hanjia Zhang¹, Shicheng Yao¹, Jingpeng Guo¹, Xiaozhen Zhang¹, Tingbo Liang², Xueli Bai³

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Hangzhou 310009, China.
² Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Hangzhou 310009, China. Electronic address: liangtingbo@zju.edu.cn.
³ Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China; MOE Joint International Research Laboratory of Pancreatic Diseases, Hangzhou 310009, China. Electronic address: shirleybai@zju.edu.cn.

PMID: 41120020
DOI: 10.1016/j.phrs.2025.108003

Abstract

Tumour progression is accompanied by metabolic reprogramming, enabling adaptation to the nutrient-deprived microenvironment. Amino acids, as key metabolic substrates, play a central role in metabolic reprogramming. Beyond their conventional metabolic roles, amino acids function as signalling molecules, activating specific (e.g., BAG2, RBM39, HDAC6, and NMDA receptor) or promiscuous (e.g., GCN2, mTORC1) sensor proteins and subsequently promoting tumour cell proliferation and survival through oncogenic signalling pathways or epigenetic modifications. This review aims to summarise the non-metabolic functions of amino acids, particularly focusing on their sensor-mediated cross-talk, to utilise their potential as novel therapeutic targets.

Keywords: Amino acid metabolism; Amino acid sensors; Cancer progression; Cancer therapy; mTORC1.

Publication types

Review

MeSH terms

Amino Acids* / metabolism
Animals
Humans
Neoplasms* / drug therapy
Neoplasms* / metabolism
Neoplasms* / pathology
Signal Transduction

Substances

Amino Acids