Pan-cancer analysis reveals TPI1 as druggable target of cancer energy metabolism switch

Abstract

Cancer metabolism is a critical aspect of tumor progression, and targeting key metabolic genes has emerged as a promising therapeutic strategy. In this study, we investigated the role of Triosephosphate Isomerase 1 (TPI1), a glycolytic enzyme, in cancer metabolism and its potential as a therapeutic target across various cancer types. By integrating pan-cancer bulk RNA-seq data from 9313 samples, single-cell RNA-seq analysis, and a genome-scale metabolic model, we systematically examined the effects of TPI1 expression on cancer metabolism, proliferation, and metastasis. Our results revealed that TPI1 is overexpressed in multiple cancers and is associated with increased production of ATP, lactate, NADPH, and glutamine, all of which play significant roles in cancer proliferation. Single-cell RNA-seq and spatial transcriptome analysis confirmed the increased expression of TPI1 in tumor cells, supporting its relevance in the tumor microenvironment. Furthermore, the genome-scale metabolic model demonstrated that high TPI1 expression correlates with increased production of critical metabolites, such as ATP, lactate, NADPH, and glutamine, which are known to be involved in cancer proliferation and metastasis. These findings collectively suggest that TPI1 could be a potential therapeutic target for cancer treatment. Further studies should focus on validating these findings in preclinical models and assessing the efficacy of TPI1 inhibitors as a novel approach for cancer therapy.