Amino acid sensing in cancer

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.