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TXNIP 在癌症中的作用：氧化还原、代谢和免疫肿瘤控制之间的精细平衡。

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

机构信息

Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, UK.

Clinical Research Center (CRC), Clinical Pathology Center (CPC), Chongqing University Three Gorges Hospital, Chongqing University, Wanzhou, Chongqing, China.

出版信息

Br J Cancer. 2023 Dec;129(12):1877-1892. doi: 10.1038/s41416-023-02442-4. Epub 2023 Oct 4.

DOI:10.1038/s41416-023-02442-4
PMID:37794178
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10703902/
Abstract

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.

摘要

硫氧还蛋白相互作用蛋白 (TXNIP) 通常被认为是细胞氧化的主要调节剂，调节硫氧还蛋白 (Trx) 的表达和功能。最近的研究表明，TXNIP 具有更广泛的其他作用：从调节葡萄糖和脂质代谢，到细胞周期停滞和炎症。它的表达被肿瘤细胞和更广泛的肿瘤微环境 (TME) 中常见的应激源所增加，因此，TXNIP 在癌症中得到了广泛的研究。在这篇综述中，我们评估了关于 TXNIP 的调节和功能的现有文献，强调了它在调节肿瘤微环境中不同细胞类型之间信号转导方面的新兴作用。然后，我们评估了该领域当前和未来的转化机会及其相关挑战。对 TXNIP 在癌症中的功能和机制的更好理解可能会增强其作为治疗靶点的适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/571d/10703902/b51ac75308d2/41416_2023_2442_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/571d/10703902/9b94127d6e30/41416_2023_2442_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/571d/10703902/57967a176fa9/41416_2023_2442_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/571d/10703902/e6d29b104752/41416_2023_2442_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/571d/10703902/76e850ec2051/41416_2023_2442_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/571d/10703902/b51ac75308d2/41416_2023_2442_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/571d/10703902/9b94127d6e30/41416_2023_2442_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/571d/10703902/57967a176fa9/41416_2023_2442_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/571d/10703902/e6d29b104752/41416_2023_2442_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/571d/10703902/76e850ec2051/41416_2023_2442_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/571d/10703902/b51ac75308d2/41416_2023_2442_Fig5_HTML.jpg

相似文献

[1]
The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control.

Br J Cancer. 2023-12

[2]
Thioredoxin interacting protein: redox dependent and independent regulatory mechanisms.

Antioxid Redox Signal. 2011-12-20

[3]
The structural basis for the negative regulation of thioredoxin by thioredoxin-interacting protein.

Nat Commun. 2014

[4]
Role of Thioredoxin-Interacting Protein in Diseases and Its Therapeutic Outlook.

Int J Mol Sci. 2021-3-9

[5]
TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook.

Oxid Med Cell Longev. 2022

[6]
Physiological and Pathophysiological Roles of Thioredoxin Interacting Protein: A Perspective on Redox Inflammation and Metabolism.

Antioxid Redox Signal. 2023-2

[7]
2-Deoxyglucose induces the expression of thioredoxin interacting protein (TXNIP) by increasing O-GlcNAcylation - Implications for targeting the Warburg effect in cancer cells.

Biochem Biophys Res Commun. 2015-10-2

[8]
Cardiomyocyte-specific Txnip C247S mutation improves left ventricular functional reserve in streptozotocin-induced diabetic mice.

Am J Physiol Heart Circ Physiol. 2021-8-1

[9]
Redox-dependent and independent effects of thioredoxin interacting protein.

Biol Chem. 2020-10-25

[10]
Thioredoxin-interacting protein: pathophysiology and emerging pharmacotherapeutics in cardiovascular disease and diabetes.

Cardiovasc Drugs Ther. 2014-8

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Trim21 deficiency alleviates osteoporosis by inhibiting osteoclast differentiation through regulating Txnip.

Arthritis Res Ther. 2025-8-1

[2]
NLRP3 Inflammasome and Inflammatory Response in Aging Disorders: The Entanglement of Redox Modulation in Different Outcomes.

Cells. 2025-6-29

[3]
Malevolent alliance of MYBL2 cancer stem cell and SPP1+ macrophage confers resistance to neoadjuvant immunotherapy in bladder cancer.

J Immunother Cancer. 2025-7-10

[4]
Exploiting mitochondrial dysfunction to overcome BRAF inhibitor resistance in advanced melanoma: the role of disulfiram as a copper ionophore.

Cell Death Dis. 2025-7-1

[5]
Research progress on the cross-regulation between ferroptosis and immunogenic cell death in tumor micro-environment.

Front Oncol. 2025-6-4

[6]
Integrative analysis of mRNA stability regulation uncovers a metastasis-suppressive program in breast cancer.

bioRxiv. 2025-6-7

[7]
HNMT Promotes the Occurrence and Progression of Nasopharyngeal Carcinoma by Inhibiting the IFN/TXNIP/p53 Axis.

Curr Med Sci. 2025-6-11

[8]
Adipocyte/Tumor cell crosstalk via IGF-1/TXNIP axis promotes malignancy and endocrine resistance in breast cancer.

Cell Commun Signal. 2025-6-3

[9]
Genome editing of TXNIP in human pluripotent stem cells for the generation of hepatocyte-like cells and insulin-producing islet-like aggregates.

Stem Cell Res Ther. 2025-5-4

[10]
Glucose deprivation and identification of TXNIP as an immunometabolic modulator of T cell activation in cancer.

Front Immunol. 2025-4-7

本文引用的文献

[1]
ATF4/TXNIP/REDD1/mTOR signaling mediates the antitumor activities of liver X receptor in pancreatic cancers.

Cancer Innov. 2022-6-30

[2]
BCR-ABL triggers a glucose-dependent survival program during leukemogenesis through the suppression of TXNIP.

Cell Death Dis. 2023-4-24

[3]
Chronic acidosis rewires cancer cell metabolism through PPARα signaling.

Int J Cancer. 2023-4-15

[4]
Thioredoxin-interacting protein-activated intracellular potassium deprivation mediates the anti-tumour effect of a novel histone acetylation inhibitor HL23, a fangchinoline derivative, in human hepatocellular carcinoma.

J Adv Res. 2023-9

[5]
Low-dose arsenite causes overexpression of EGF, TGFα, and HSP90 through Trx1-TXNIP-NLRP3 axis mediated signaling pathways in the human bladder epithelial cells.

Ecotoxicol Environ Saf. 2022-12-1

[6]
miR-148a-3p and DDX6 functional link promotes survival of myeloid leukemia cells.

Blood Adv. 2023-8-8

[7]
TXNIP inhibits the progression of osteosarcoma through DDIT4-mediated mTORC1 suppression.

Am J Cancer Res. 2022-8-15

[8]
Blocking CHOP-dependent TXNIP shuttling to mitochondria attenuates albuminuria and mitigates kidney injury in nephrotic syndrome.

Proc Natl Acad Sci U S A. 2022-8-30

[9]
ADAMTS10 inhibits aggressiveness via JAK/STAT/c-MYC pathway and reprograms macrophage to create an anti-malignant microenvironment in gastric cancer.

Gastric Cancer. 2022-11

[10]
Targeted Induction of Endogenous VDUP1 by Small Activating RNA Inhibits the Growth of Lung Cancer Cells.

Int J Mol Sci. 2022-7-13

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