TLR/WNT: A Novel Relationship in Immunomodulation of Lung Cancer

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Jun 24

PMID 35742983

Authors

Aina Martin-Medina

Noemi Ceron-Pisa

Esther Martinez-Font

Hanaa Shafiek

Antonia Obrador-Hevia

Jaume Sauleda

Amanda Iglesias

Affiliations

Soon will be listed here.

Abstract

The most frequent cause of death by cancer worldwide is lung cancer, and the 5-year survival rate is still very poor for patients with advanced stage. Understanding the crosstalk between the signaling pathways that are involved in disease, especially in metastasis, is crucial to developing new targeted therapies. Toll-like receptors (TLRs) are master regulators of the immune responses, and their dysregulation in lung cancer is linked to immune escape and promotes tumor malignancy by facilitating angiogenesis and proliferation. On the other hand, over-activation of the WNT signaling pathway has been reported in lung cancer and is also associated with tumor metastasis via induction of Epithelial-to-mesenchymal-transition (EMT)-like processes. An interaction between both TLRs and the WNT pathway was discovered recently as it was found that the TLR pathway can be activated by WNT ligands in the tumor microenvironment; however, the implications of such interactions in the context of lung cancer have not been discussed yet. Here, we offer an overview of the interaction of TLR-WNT in the lung and its potential implications and role in the oncogenic process.

Citing Articles

Machine learning-derived peripheral blood transcriptomic biomarkers for early lung cancer diagnosis: Unveiling tumor-immune interaction mechanisms.

Li X, Li X, Qin J, Lei L, Guo H, Zheng X Biofactors. 2024; 51(1):e2129.

PMID: 39415336 PMC: 11681315. DOI: 10.1002/biof.2129.

A comprehensive review of Sjögren's syndrome: Classification criteria, risk factors, and signaling pathways.

Zhao T, Zhang R, Li Z, Qin D, Wang X Heliyon. 2024; 10(17):e36220.

PMID: 39286095 PMC: 11403439. DOI: 10.1016/j.heliyon.2024.e36220.

Toll-like Receptors: Key Players in Squamous Cell Carcinoma Progression.

Smok-Kalwat J, Mertowska P, Mertowski S, Gozdz S, Grywalska E J Clin Med. 2024; 13(15).

PMID: 39124797 PMC: 11313009. DOI: 10.3390/jcm13154531.

Interplay between WNT/PI3K-mTOR axis and the microbiota in APC-driven colorectal carcinogenesis: data from a pilot study and possible implications for CRC prevention.

Di Paola F, Alquati C, Conti G, Calafato G, Turroni S, DAmico F J Transl Med. 2024; 22(1):631.

PMID: 38970018 PMC: 11227240. DOI: 10.1186/s12967-024-05305-5.

Analysis of Selected Toll-like Receptors in the Pathogenesis and Advancement of Non-Small-Cell Lung Cancer.

Smok-Kalwat J, Mertowska P, Mertowski S, Gozdz S, Korona-Glowniak I, Kwasniewski W J Clin Med. 2024; 13(10).

PMID: 38792335 PMC: 11122486. DOI: 10.3390/jcm13102793.

References

Yuan K, Shamskhou E, Orcholski M, Nathan A, Reddy S, Honda H . Loss of Endothelium-Derived Wnt5a Is Associated With Reduced Pericyte Recruitment and Small Vessel Loss in Pulmonary Arterial Hypertension. Circulation. 2018; 139(14):1710-1724. PMC: 6443444. DOI: 10.1161/CIRCULATIONAHA.118.037642. View

Nguyen D, Chiang A, Zhang X, Kim J, Kris M, Ladanyi M . WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis. Cell. 2009; 138(1):51-62. PMC: 2742946. DOI: 10.1016/j.cell.2009.04.030. View

Pradere J, Dapito D, Schwabe R . The Yin and Yang of Toll-like receptors in cancer. Oncogene. 2013; 33(27):3485-95. PMC: 4059777. DOI: 10.1038/onc.2013.302. View

Lemjabbar-Alaoui H, Hassan O, Yang Y, Buchanan P . Lung cancer: Biology and treatment options. Biochim Biophys Acta. 2015; 1856(2):189-210. PMC: 4663145. DOI: 10.1016/j.bbcan.2015.08.002. View

Wang Z, Tu K, Xia L, Luo K, Luo W, Tang J . The Open Chromatin Landscape of Non-Small Cell Lung Carcinoma. Cancer Res. 2019; 79(19):4840-4854. DOI: 10.1158/0008-5472.CAN-18-3663. View

Akiri G, Cherian M, Vijayakumar S, Liu G, Bafico A, Aaronson S . Wnt pathway aberrations including autocrine Wnt activation occur at high frequency in human non-small-cell lung carcinoma. Oncogene. 2009; 28(21):2163-72. PMC: 4451819. DOI: 10.1038/onc.2009.82. View

Mittal D, Saccheri F, Venereau E, Pusterla T, Bianchi M, Rescigno M . TLR4-mediated skin carcinogenesis is dependent on immune and radioresistant cells. EMBO J. 2010; 29(13):2242-52. PMC: 2905255. DOI: 10.1038/emboj.2010.94. View

Konigshoff M, Balsara N, Pfaff E, Kramer M, Chrobak I, Seeger W . Functional Wnt signaling is increased in idiopathic pulmonary fibrosis. PLoS One. 2008; 3(5):e2142. PMC: 2374879. DOI: 10.1371/journal.pone.0002142. View

Igney F, Krammer P . Immune escape of tumors: apoptosis resistance and tumor counterattack. J Leukoc Biol. 2002; 71(6):907-20. View

10.

Li X, Jiang S, Tapping R . Toll-like receptor signaling in cell proliferation and survival. Cytokine. 2009; 49(1):1-9. PMC: 2808458. DOI: 10.1016/j.cyto.2009.08.010. View

11.

Hussain M, Rao M, Humphries A, Hong J, Liu F, Yang M . Tobacco smoke induces polycomb-mediated repression of Dickkopf-1 in lung cancer cells. Cancer Res. 2009; 69(8):3570-8. PMC: 8374472. DOI: 10.1158/0008-5472.CAN-08-2807. View

12.

Chin A, Miyahira A, Covarrubias A, Teague J, Guo B, Dempsey P . Toll-like receptor 3-mediated suppression of TRAMP prostate cancer shows the critical role of type I interferons in tumor immune surveillance. Cancer Res. 2010; 70(7):2595-603. PMC: 2995454. DOI: 10.1158/0008-5472.CAN-09-1162. View

13.

Di Lorenzo A, Bolli E, Tarone L, Cavallo F, Conti L . Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota. Int J Mol Sci. 2020; 21(24). PMC: 7763461. DOI: 10.3390/ijms21249418. View

14.

Fukata M, Hernandez Y, Conduah D, Cohen J, Chen A, Breglio K . Innate immune signaling by Toll-like receptor-4 (TLR4) shapes the inflammatory microenvironment in colitis-associated tumors. Inflamm Bowel Dis. 2009; 15(7):997-1006. PMC: 2712657. DOI: 10.1002/ibd.20880. View

15.

MacDonald B, Tamai K, He X . Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009; 17(1):9-26. PMC: 2861485. DOI: 10.1016/j.devcel.2009.06.016. View

16.

Hasan U, Trinchieri G, Vlach J . Toll-like receptor signaling stimulates cell cycle entry and progression in fibroblasts. J Biol Chem. 2005; 280(21):20620-7. DOI: 10.1074/jbc.M500877200. View

17.

Grivennikov S, Karin M . Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stage. Ann Rheum Dis. 2011; 70 Suppl 1:i104-8. DOI: 10.1136/ard.2010.140145. View

18.

Martin-Medina A, Lehmann M, Burgy O, Hermann S, Baarsma H, Wagner D . Increased Extracellular Vesicles Mediate WNT5A Signaling in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2018; 198(12):1527-1538. DOI: 10.1164/rccm.201708-1580OC. View

19.

Rhee S, Im E, Pothoulakis C . Toll-like receptor 5 engagement modulates tumor development and growth in a mouse xenograft model of human colon cancer. Gastroenterology. 2008; 135(2):518-28. PMC: 2667819. DOI: 10.1053/j.gastro.2008.04.022. View

20.

Vesel M, Rapp J, Feller D, Kiss E, Jaromi L, Meggyes M . ABCB1 and ABCG2 drug transporters are differentially expressed in non-small cell lung cancers (NSCLC) and expression is modified by cisplatin treatment via altered Wnt signaling. Respir Res. 2017; 18(1):52. PMC: 5364604. DOI: 10.1186/s12931-017-0537-6. View