Uncovering Novel Mechanisms of Chitinase-3-like Protein 1 in Driving Inflammation-associated Cancers

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2024 Jul 27

PMID 39068486

Authors

Yan Fan

Yuan Meng

Xingwei Hu

Jianhua Liu

Xiaosong Qin

Affiliations

Soon will be listed here.

Abstract

Chitinase-3-like protein 1 (CHI3L1) is a secreted glycoprotein that is induced and regulated by multiple factors during inflammation in enteritis, pneumonia, asthma, arthritis, and other diseases. It is associated with the deterioration of the inflammatory environment in tissues with chronic inflammation caused by microbial infection or autoimmune diseases. The expression of CHI3L1 expression is upregulated in several malignant tumors, underscoring the crucial role of chronic inflammation in the initiation and progression of cancer. While the precise mechanism connecting inflammation and cancer is unclear, the involvement of CHI3L1 is involved in chronic inflammation, suggesting its role as a contributing factor to in the link between inflammation and cancer. CHI3L1 can aggravate DNA oxidative damage, induce the cancerous phenotype, promote the development of a tumor inflammatory environment and angiogenesis, inhibit immune cells, and promote cancer cell growth, invasion, and migration. Furthermore, it participates in the initiation of cancer progression and metastasis by binding with transmembrane receptors to mediate intracellular signal transduction. Based on the current research on CHI3L1, we explore introduce the receptors that interact with CHI3L1 along with the signaling pathways that may be triggered during chronic inflammation to enhance tumorigenesis and progression. In the last section of the article, we provide a brief overview of anti-inflammatory therapies that target CHI3L1.

Citing Articles

Chitinase-3 Like-Protein-1 Signature in Neurological Disorders: Emphasis on Stroke.

Mathias K, Machado R, Andrade N, Piacentini N, Martins C, Prophiro J J Mol Neurosci. 2025; 75(1):25.

PMID: 39976746 DOI: 10.1007/s12031-025-02311-0.

Chitinase-3-like-1: a multifaceted player in neuroinflammation and degenerative pathologies with therapeutic implications.

Mwale P, Hsieh C, Yen T, Jan J, Taliyan R, Yang C Mol Neurodegener. 2025; 20(1):7.

PMID: 39827337 PMC: 11742494. DOI: 10.1186/s13024-025-00801-8.

References

Chen K, Li D, Lu T, Chang S . Structural Characterization of the CD44 Stem Region for Standard and Cancer-Associated Isoforms. Int J Mol Sci. 2020; 21(1). PMC: 6982006. DOI: 10.3390/ijms21010336. View

Song N, Zhang Y, Kong F, Yang H, Ma X . HOXA-AS2 promotes type I endometrial carcinoma via miRNA-302c-3p-mediated regulation of ZFX. Cancer Cell Int. 2020; 20:359. PMC: 7393821. DOI: 10.1186/s12935-020-01443-0. View

Rutter M, Saunders B, Wilkinson K, Rumbles S, Schofield G, Kamm M . Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004; 126(2):451-9. DOI: 10.1053/j.gastro.2003.11.010. View

Suzuki H, Boki H, Kamijo H, Nakajima R, Oka T, Shishido-Takahashi N . YKL-40 Promotes Proliferation of Cutaneous T-Cell Lymphoma Tumor Cells through Extracellular Signal-Regulated Kinase Pathways. J Invest Dermatol. 2019; 140(4):860-868.e3. DOI: 10.1016/j.jid.2019.09.007. View

Zhao Y, Vanderkooi S, Kan F . The role of oviduct-specific glycoprotein (OVGP1) in modulating biological functions of gametes and embryos. Histochem Cell Biol. 2022; 157(3):371-388. PMC: 8979936. DOI: 10.1007/s00418-021-02065-x. View

Kui L, Kim A, Onyuru J, Hoffman H, Feldstein A . BRP39 Regulates Neutrophil Recruitment in NLRP3 Inflammasome-Induced Liver Inflammation. Cell Mol Gastroenterol Hepatol. 2023; 17(3):481-497. PMC: 10837621. DOI: 10.1016/j.jcmgh.2023.12.002. View

Kawada M, Seno H, Kanda K, Nakanishi Y, Akitake R, Komekado H . Chitinase 3-like 1 promotes macrophage recruitment and angiogenesis in colorectal cancer. Oncogene. 2011; 31(26):3111-23. PMC: 3290745. DOI: 10.1038/onc.2011.498. View

Carr L, Jacobson S, Lynch D, Foreman M, Flenaugh E, Hersh C . Features of COPD as Predictors of Lung Cancer. Chest. 2018; 153(6):1326-1335. PMC: 6026288. DOI: 10.1016/j.chest.2018.01.049. View

Kzhyshkowska J, Larionova I, Liu T . YKL-39 as a Potential New Target for Anti-Angiogenic Therapy in Cancer. Front Immunol. 2020; 10:2930. PMC: 6988383. DOI: 10.3389/fimmu.2019.02930. View

10.

Abu-Freha N, Cohen B, Gordon M, Weissmann S, Kestenbaum E, Vosko S . Colorectal cancer among inflammatory bowel disease patients: risk factors and prevalence compared to the general population. Front Med (Lausanne). 2023; 10:1225616. PMC: 10443703. DOI: 10.3389/fmed.2023.1225616. View

11.

Zhang W, Chen S, Zhou S, Wu S, Wang H . Inflammasomes and Fibrosis. Front Immunol. 2021; 12:643149. PMC: 8226128. DOI: 10.3389/fimmu.2021.643149. View

12.

Ngernyuang N, Yan W, Schwartz L, Oh D, Liu Y, Chen H . A Heparin Binding Motif Rich in Arginine and Lysine is the Functional Domain of YKL-40. Neoplasia. 2017; 20(2):182-192. PMC: 5773473. DOI: 10.1016/j.neo.2017.11.011. View

13.

Mitchell H, Drake M, Medley G . Prospective evaluation of risk of cervical cancer after cytological evidence of human papilloma virus infection. Lancet. 1986; 1(8481):573-5. DOI: 10.1016/s0140-6736(86)92807-2. View

14.

Greten F, Eckmann L, Greten T, Park J, Li Z, Egan L . IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell. 2004; 118(3):285-96. DOI: 10.1016/j.cell.2004.07.013. View

15.

Hao H, Chen H, Xie L, Liu H . YKL-40 promotes invasion and metastasis of bladder cancer by regulating epithelial mesenchymal transition. Ann Med. 2021; 53(1):1170-1178. PMC: 8281123. DOI: 10.1080/07853890.2021.1950920. View

16.

Hwang H, Park S, Cheon E, Lee M, Kim H . Fibronectin fragment-induced expression of matrix metalloproteinases is mediated by MyD88-dependent TLR-2 signaling pathway in human chondrocytes. Arthritis Res Ther. 2015; 17:320. PMC: 4643537. DOI: 10.1186/s13075-015-0833-9. View

17.

Bertelsen T, Ljungberg C, Kjellerup R, Iversen L, Johansen C . IL-17F regulates psoriasis-associated genes through IκBζ. Exp Dermatol. 2016; 26(3):234-241. DOI: 10.1111/exd.13182. View

18.

Fan J, Zhou Z, Luo Y, Luo Q, Chen S, Zhao J . Exosomal lncRNA NEAT1 from cancer-associated fibroblasts facilitates endometrial cancer progression via miR-26a/b-5p-mediated STAT3/YKL-40 signaling pathway. Neoplasia. 2021; 23(7):692-703. PMC: 8233173. DOI: 10.1016/j.neo.2021.05.004. View

19.

Hudson B, Carter A, Harja E, Kalea A, Arriero M, Yang H . Identification, classification, and expression of RAGE gene splice variants. FASEB J. 2007; 22(5):1572-80. DOI: 10.1096/fj.07-9909com. View

20.

Greenstein A, Sachar D, Smith H, Pucillo A, Papatestas A, KREEL I . Cancer in universal and left-sided ulcerative colitis: factors determining risk. Gastroenterology. 1979; 77(2):290-4. View