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The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control

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BRITISH JOURNAL OF CANCER
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DOI: 10.1038/s41416-023-02442-4

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TXNIP is a master regulator of cellular oxidation, and recent studies have revealed its additional roles in metabolism, cell cycle, and inflammation. It is extensively studied in cancers, particularly in modulating signaling between different cell types within the tumor microenvironment. Further understanding of TXNIP's functions and mechanisms in cancer may enhance its potential as a therapeutic target.
Thioredoxin-interacting protein (TXNIP) is commonly considered a master regulator of cellular oxidation, regulating the expression and function of Thioredoxin (Trx). Recent work has identified that TXNIP has a far wider range of additional roles: from regulating glucose and lipid metabolism, to cell cycle arrest and inflammation. Its expression is increased by stressors commonly found in neoplastic cells and the wider tumor microenvironment (TME), and, as such, TXNIP has been extensively studied in cancers. In this review, we evaluate the current literature regarding the regulation and the function of TXNIP, highlighting its emerging role in modulating signaling between different cell types within the TME. We then assess current and future translational opportunities and the associated challenges in this area. An improved understanding of the functions and mechanisms of TXNIP in cancers may enhance its suitability as a therapeutic target.

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