Wnt/beta-catenin Pathway: Modulating Anticancer Immune Response

Overview

Journal J Hematol Oncol

Publisher Biomed Central

Specialties Hematology
Oncology

Date 2017 May 7

PMID 28476164

Citations 329

Authors

Sachin Gopalkrishna Pai

Benedito A Carneiro

Jose Mauricio Mota

Ricardo Costa

Caio Abner Leite

Romualdo Barroso-Sousa

Jason Benjamin Kaplan

Young Kwang Chae

Francis Joseph Giles

Affiliations

Soon will be listed here.

Abstract

Wnt/β-catenin signaling, a highly conserved pathway through evolution, regulates key cellular functions including proliferation, differentiation, migration, genetic stability, apoptosis, and stem cell renewal. The Wnt pathway mediates biological processes by a canonical or noncanonical pathway, depending on the involvement of β-catenin in signal transduction. β-catenin is a core component of the cadherin protein complex, whose stabilization is essential for the activation of Wnt/β-catenin signaling. As multiple aberrations in this pathway occur in numerous cancers, WNT-directed therapy represents an area of significant developmental therapeutics focus. The recently described role of Wnt/β-catenin pathway in regulating immune cell infiltration of the tumor microenvironment renewed the interest, given its potential impact on responses to immunotherapy treatments. This article summarizes the role of Wnt/β-catenin pathway in cancer and ongoing therapeutic strategies involving this pathway.

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References

Safholm A, Tuomela J, Rosenkvist J, Dejmek J, Harkonen P, Andersson T . The Wnt-5a-derived hexapeptide Foxy-5 inhibits breast cancer metastasis in vivo by targeting cell motility. Clin Cancer Res. 2008; 14(20):6556-63. DOI: 10.1158/1078-0432.CCR-08-0711. View

Dickson C, Peters G . Potential oncogene product related to growth factors. Nature. 1987; 326(6116):833. DOI: 10.1038/326833a0. View

Eguchi M, Nguyen C, Lee S, Kahn M . ICG-001, a novel small molecule regulator of TCF/beta-catenin transcription. Med Chem. 2006; 1(5):467-72. DOI: 10.2174/1573406054864098. View

Nusse R, Varmus H . Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982; 31(1):99-109. DOI: 10.1016/0092-8674(82)90409-3. View

Veeman M, Axelrod J, Moon R . A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. Dev Cell. 2003; 5(3):367-77. DOI: 10.1016/s1534-5807(03)00266-1. View

Alves C, Ober-Blobaum J, Brouwers-Haspels I, Asmawidjaja P, Mus A, Razawy W . Dendritic Cell-Specific Deletion of β-Catenin Results in Fewer Regulatory T-Cells without Exacerbating Autoimmune Collagen-Induced Arthritis. PLoS One. 2015; 10(11):e0142972. PMC: 4654567. DOI: 10.1371/journal.pone.0142972. View

van Amerongen R, Nusse R . Towards an integrated view of Wnt signaling in development. Development. 2009; 136(19):3205-14. DOI: 10.1242/dev.033910. View

Boulter L, Guest R, Kendall T, Wilson D, Wojtacha D, Robson A . WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. J Clin Invest. 2015; 125(3):1269-85. PMC: 4362247. DOI: 10.1172/JCI76452. View

Konsavage Jr W, Kyler S, Rennoll S, Jin G, Yochum G . Wnt/β-catenin signaling regulates Yes-associated protein (YAP) gene expression in colorectal carcinoma cells. J Biol Chem. 2012; 287(15):11730-9. PMC: 3320921. DOI: 10.1074/jbc.M111.327767. View

10.

Merino V, Cho S, Liang X, Park S, Jin K, Chen Q . Inhibitors of STAT3, β-catenin, and IGF-1R sensitize mouse PIK3CA-mutant breast cancer to PI3K inhibitors. Mol Oncol. 2017; 11(5):552-566. PMC: 5527464. DOI: 10.1002/1878-0261.12053. View

11.

Chiang J, Chou Y, Chen T, Ng K, Lin J . Nuclear beta-catenin expression is closely related to ulcerative growth of colorectal carcinoma. Br J Cancer. 2002; 86(7):1124-9. PMC: 2364167. DOI: 10.1038/sj.bjc.6600214. View

12.

Wickstrom M, Dyberg C, Milosevic J, Einvik C, Calero R, Sveinbjornsson B . Wnt/β-catenin pathway regulates MGMT gene expression in cancer and inhibition of Wnt signalling prevents chemoresistance. Nat Commun. 2015; 6:8904. PMC: 4674781. DOI: 10.1038/ncomms9904. View

13.

Heidel F, Bullinger L, Feng Z, Wang Z, Neff T, Stein L . Genetic and pharmacologic inhibition of β-catenin targets imatinib-resistant leukemia stem cells in CML. Cell Stem Cell. 2012; 10(4):412-24. PMC: 3339412. DOI: 10.1016/j.stem.2012.02.017. View

14.

Lazarevic B, Hammarstrom C, Yang J, Ramberg H, Diep L, Karlsen S . The effects of short-term genistein intervention on prostate biomarker expression in patients with localised prostate cancer before radical prostatectomy. Br J Nutr. 2012; 108(12):2138-47. DOI: 10.1017/S0007114512000384. View

15.

Miranda M, Galli L, Enriquez M, Szabo L, Gao X, Hannoush R . Identification of the WNT1 residues required for palmitoylation by Porcupine. FEBS Lett. 2014; 588(24):4815-24. PMC: 4268045. DOI: 10.1016/j.febslet.2014.11.016. View

16.

Gattinoni L, Ji Y, Restifo N . Wnt/beta-catenin signaling in T-cell immunity and cancer immunotherapy. Clin Cancer Res. 2010; 16(19):4695-701. PMC: 3393131. DOI: 10.1158/1078-0432.CCR-10-0356. View

17.

Riese J, Yu X, Munnerlyn A, Eresh S, Hsu S, Grosschedl R . LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic. Cell. 1997; 88(6):777-87. DOI: 10.1016/s0092-8674(00)81924-8. View

18.

Gajewski T . The Next Hurdle in Cancer Immunotherapy: Overcoming the Non-T-Cell-Inflamed Tumor Microenvironment. Semin Oncol. 2015; 42(4):663-71. PMC: 4555998. DOI: 10.1053/j.seminoncol.2015.05.011. View

19.

Bos C, Kodach L, van den Brink G, Diks S, van Santen M, Richel D . Effect of aspirin on the Wnt/beta-catenin pathway is mediated via protein phosphatase 2A. Oncogene. 2006; 25(49):6447-56. DOI: 10.1038/sj.onc.1209658. View

20.

Spranger S, Bao R, Gajewski T . Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature. 2015; 523(7559):231-5. DOI: 10.1038/nature14404. View