Wnt Signaling in the Regulation of Immune Cell and Cancer Therapeutics

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2019 Nov 6

PMID 31684152

Citations 53

Authors

Muhammad Haseeb

Rameez Hassan Pirzada

Qurat Ul Ain

Sangdun Choi

Affiliations

Soon will be listed here.

Abstract

Wnt signaling is one of the important pathways to play a major role in various biological processes, such as embryonic stem-cell development, tissue regeneration, cell differentiation, and immune cell regulation. Recent studies suggest that Wnt signaling performs an essential function in immune cell modulation and counteracts various disorders. Nonetheless, the emerging role and mechanism of action of this signaling cascade in immune cell regulation, as well as its involvement in various cancers, remain debatable. The Wnt signaling in immune cells is very diverse, e.g., the tolerogenic role of dendritic cells, the development of natural killer cells, thymopoiesis of T cells, B-cell-driven initiation of T-cells, and macrophage actions in tissue repair, regeneration, and fibrosis. The purpose of this review is to highlight the current therapeutic targets in (and the prospects of) Wnt signaling, as well as the potential suitability of available modulators for the development of cancer immunotherapies. Although there are several Wnt inhibitors relevant to cancer, it would be worthwhile to extend this approach to immune cells.

Citing Articles

AS03-adjuvanted H5N1 vaccine enhances immune response by modulating NR4A1, SDC1, ID3 genes, and reducing cortisol.

Jin L, Li J, Zhu F Hum Vaccin Immunother. 2024; 20(1):2426319.

PMID: 39569615 PMC: 11583616. DOI: 10.1080/21645515.2024.2426319.

Systematic Analysis of miR-506-3p Target Genes Identified Key Mediators of Its Differentiation-Inducing Function.

Cardus D, Smith M, Vernaza A, Smith J, Del Buono B, Parajuli A Genes (Basel). 2024; 15(10).

PMID: 39457392 PMC: 11507652. DOI: 10.3390/genes15101268.

Unraveling Cancer's Wnt Signaling: Dynamic Control through Protein Kinase Regulation.

Tumen D, Heumann P, Huber J, Hahn N, Macek C, Ernst M Cancers (Basel). 2024; 16(15).

PMID: 39123414 PMC: 11312265. DOI: 10.3390/cancers16152686.

Diagnostic and prognostic significance of circulating secreted frizzled-related protein 5 in colorectal cancer.

Li R, Liu S, Yeo K, Edwards S, Li M, Santos R Cancer Med. 2024; 13(11):e7352.

PMID: 38872420 PMC: 11176579. DOI: 10.1002/cam4.7352.

Wnt signaling and tumors (Review).

Wang H, Zhang L, Hu C, Li H, Jiang M Mol Clin Oncol. 2024; 21(1):45.

PMID: 38798312 PMC: 11117032. DOI: 10.3892/mco.2024.2743.

References

Swafford D, Manicassamy S . Wnt signaling in dendritic cells: its role in regulation of immunity and tolerance. Discov Med. 2015; 19(105):303-10. PMC: 4513356. View

Park Y, Bochner B . Eosinophil survival and apoptosis in health and disease. Allergy Asthma Immunol Res. 2010; 2(2):87-101. PMC: 2846745. DOI: 10.4168/aair.2010.2.2.87. View

Manoharan I, Hong Y, Suryawanshi A, Angus-Hill M, Sun Z, Mellor A . TLR2-dependent activation of β-catenin pathway in dendritic cells induces regulatory responses and attenuates autoimmune inflammation. J Immunol. 2014; 193(8):4203-13. PMC: 4185231. DOI: 10.4049/jimmunol.1400614. View

Manicassamy S, Reizis B, Ravindran R, Nakaya H, Salazar-Gonzalez R, Wang Y . Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science. 2010; 329(5993):849-53. PMC: 3732486. DOI: 10.1126/science.1188510. View

Vacchio M, Wang L, Bouladoux N, Carpenter A, Xiong Y, Williams L . A ThPOK-LRF transcriptional node maintains the integrity and effector potential of post-thymic CD4+ T cells. Nat Immunol. 2014; 15(10):947-56. PMC: 4251968. DOI: 10.1038/ni.2960. View

Chan-On W, Nairismagi M, Ong C, Lim W, Dima S, Pairojkul C . Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nat Genet. 2013; 45(12):1474-8. DOI: 10.1038/ng.2806. View

Grzywacz B, Kataria N, Kataria N, Blazar B, Miller J, Verneris M . Natural killer-cell differentiation by myeloid progenitors. Blood. 2010; 117(13):3548-58. PMC: 3072878. DOI: 10.1182/blood-2010-04-281394. View

Gonsalves F, Klein K, Carson B, Katz S, Ekas L, Evans S . An RNAi-based chemical genetic screen identifies three small-molecule inhibitors of the Wnt/wingless signaling pathway. Proc Natl Acad Sci U S A. 2011; 108(15):5954-63. PMC: 3076864. DOI: 10.1073/pnas.1017496108. View

Schoumacher M, Hurov K, Lehar J, Yan-Neale Y, Mishina Y, Sonkin D . Inhibiting Tankyrases sensitizes KRAS-mutant cancer cells to MEK inhibitors via FGFR2 feedback signaling. Cancer Res. 2014; 74(12):3294-305. DOI: 10.1158/0008-5472.CAN-14-0138-T. View

10.

Shen M, Wang J, Ren X . New Insights into Tumor-Infiltrating B Lymphocytes in Breast Cancer: Clinical Impacts and Regulatory Mechanisms. Front Immunol. 2018; 9:470. PMC: 5852074. DOI: 10.3389/fimmu.2018.00470. View

11.

Ranheim E, Kwan H, Reya T, Wang Y, Weissman I, Francke U . Frizzled 9 knock-out mice have abnormal B-cell development. Blood. 2004; 105(6):2487-94. DOI: 10.1182/blood-2004-06-2334. View

12.

Zhou H, Mak P, Mu H, Mak D, Zeng Z, Cortes J . Combined inhibition of β-catenin and Bcr-Abl synergistically targets tyrosine kinase inhibitor-resistant blast crisis chronic myeloid leukemia blasts and progenitors in vitro and in vivo. Leukemia. 2017; 31(10):2065-2074. PMC: 5628102. DOI: 10.1038/leu.2017.87. View

13.

Qian C, Qian L, Yu Y, An H, Guo Z, Han Y . Fas signal promotes the immunosuppressive function of regulatory dendritic cells via the ERK/β-catenin pathway. J Biol Chem. 2013; 288(39):27825-35. PMC: 3784698. DOI: 10.1074/jbc.M112.425751. View

14.

Lepourcelet M, Chen Y, France D, Wang H, Crews P, Petersen F . Small-molecule antagonists of the oncogenic Tcf/beta-catenin protein complex. Cancer Cell. 2004; 5(1):91-102. DOI: 10.1016/s1535-6108(03)00334-9. View

15.

Solzak J, Atale R, Hancock B, Sinn A, Pollok K, Jones D . Dual PI3K and Wnt pathway inhibition is a synergistic combination against triple negative breast cancer. NPJ Breast Cancer. 2017; 3:17. PMC: 5460220. DOI: 10.1038/s41523-017-0016-8. View

16.

Yao H, Ashihara E, Strovel J, Nakagawa Y, Kuroda J, Nagao R . AV-65, a novel Wnt/β-catenin signal inhibitor, successfully suppresses progression of multiple myeloma in a mouse model. Blood Cancer J. 2012; 1(11):e43. PMC: 3256754. DOI: 10.1038/bcj.2011.41. View

17.

Moon R, Kohn A, De Ferrari G, Kaykas A . WNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet. 2004; 5(9):691-701. DOI: 10.1038/nrg1427. View

18.

Yamaguchi T, Nishijima M, Tashiro K, Kawabata K . Wnt--Catenin Signaling Promotes the Maturation of Mast Cells. Biomed Res Int. 2016; 2016:2048987. PMC: 5097791. DOI: 10.1155/2016/2048987. View

19.

Manicassamy S, Ravindran R, Deng J, Oluoch H, Denning T, Kasturi S . Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity. Nat Med. 2009; 15(4):401-9. PMC: 2768543. DOI: 10.1038/nm.1925. View

20.

Schiefer L, Visweswaran M, Perumal V, Arfuso F, Groth D, Newsholme P . Epigenetic regulation of the secreted frizzled-related protein family in human glioblastoma multiforme. Cancer Gene Ther. 2014; 21(7):297-303. DOI: 10.1038/cgt.2014.30. View