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Review
. 2022 Nov 10;10(11):1902.
doi: 10.3390/vaccines10111902.

Immunomodulatory Role of Thioredoxin Interacting Protein in Cancer's Impediments: Current Understanding and Therapeutic Implications

Ramkumar Katturajan  1 , Sangeetha Nithiyanandam  1 , Manisha Parthasarathy  1 , Abilash Valsala Gopalakrishnan  1 , Ezhaveni Sathiyamoorthi  2 , Jintae Lee  2 , Thiyagarajan Ramesh  3 , Mahalaxmi Iyer  4 , Sabina Evan Prince  1 , Raja Ganesan  5
Affiliations
Review

Immunomodulatory Role of Thioredoxin Interacting Protein in Cancer's Impediments: Current Understanding and Therapeutic Implications

Ramkumar Katturajan et al. Vaccines (Basel). .

Abstract

Cancer, which killed ten million people in 2020, is expected to become the world's leading health problem and financial burden. Despite the development of effective therapeutic approaches, cancer-related deaths have increased by 25.4% in the last ten years. Current therapies promote apoptosis and oxidative stress DNA damage and inhibit inflammatory mediators and angiogenesis from providing temporary relief. Thioredoxin-binding protein (TXNIP) causes oxidative stress by inhibiting the function of the thioredoxin system. It is an important regulator of many redox-related signal transduction pathways in cells. In cancer cells, it functions as a tumor suppressor protein that inhibits cell proliferation. In addition, TXNIP levels in hemocytes increased after immune stimulation, suggesting that TXNIP plays an important role in immunity. Several studies have provided experimental evidence for the immune modulatory role of TXNIP in cancer impediments. TXNIP also has the potential to act against immune cells in cancer by mediating the JAK-STAT, MAPK, and PI3K/Akt pathways. To date, therapies targeting TXNIP in cancer are still under investigation. This review highlights the role of TXNIP in preventing cancer, as well as recent reports describing its functions in various immune cells, signaling pathways, and promoting action against cancer.

Keywords: AMPK; JAK-STAT; PI3K/Akt; TXNIP; cancer; immune cells; immunomodulation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mechanistic actions of TXNIP on different immune cells drive cancer impediments. Note: Th17: T-helper 17; HIF: Hypoxia-inducible factors; GLUT1: glucose transporter 1; TXNIP: Thioredoxin-interacting protein; Trx: Thioredoxin; ROS: Reactive oxygen species; NAD+: Nicotinamide adenine dinucleotide; G6P: Glucose 6 phosphate; PPP: Pentose phosphate pathway; IL: Interleukin; NADPH: Nicotinamide adenine dinucleotide phosphate; PAX: Paired box protein; MIF: Macrophage inhibiting factor; NF-κB: Nuclear factor kappa B; NLRP: NLR family pyrin domain containing; HDAC: histone deacetylases.
Figure 2
Figure 2
The systematic illustration of TXNIP suppression in cancer progression.
Figure 3
Figure 3
Schematic representation of TXNIP in mediating signaling pathway in cancer impediments. This picture represents how TXNIP is involved in cancer suppression via JAK/STAT, AMPK/mTOR, and PI3K/AKT signaling pathways. Note: Interleukins; JAK: Janus kinase; STAT: signal transducer and activator of transcription; HIF: Hypoxia-inducible factors; TXNIP: Thioredoxin-interacting protein; Trx: Thioredoxin; PI3K: Phosphatidylinositol 3 kinase; AKT: Protein Kinase B; RTK: Receptor tyrosine kinase; KCNK3: Potassium Channel, Subfamily K, Member 3; AMPK: AMP-activated protein kinase; mTOR: Mammalian target of rapamycin; GLUT1: Glucose transporter 1; G: Glucose; G6P: Glucose 6 phosphate; K: Potassium; p: Phosphorylation. The black line/arrow represents the regulating pathway, and the blue line represents the inhibitory role.
See this image and copyright information in PMC

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