The Role of Collagen Triple Helix Repeat Containing 1 (CTHRC1) in Cancer Development and Progression

Overview

Journal Expert Opin Ther Targets

Publisher Informa Healthcare

Specialty Pharmacology

Date 2024 Apr 30

PMID 38686865

Authors

Chandra K Singh

Sofia Fernandez

Gagan Chhabra

Gabriella R Zaemisch

Ayaan Nihal

Jenna Swanlund

Naveed Ansari

Zan Said

Hao Chang

Nihal Ahmad

Affiliations

Soon will be listed here.

Abstract

Introduction: Collagen triple helix repeat containing 1 (CTHRC1) is a protein that has been implicated in pro-migratory pathways, arterial tissue-repair processes, and inhibition of collagen deposition via the regulation of multiple signaling cascades. Studies have also demonstrated an upregulation of CTHRC1 in multiple cancers where it has been linked to enhanced proliferation, invasion, and metastasis. However, the understanding of the exact role and mechanisms of CTHRC1 in cancer is far from complete.

Areas Covered: This review focuses on analyzing the role of CTHRC1 in cancer as well as its associations with clinicopathologies and cancer-related processes and signaling. We have also summarized the available literature information regarding the role of CTHRC1 in tumor microenvironment and immune signaling. Finally, we have discussed the mechanisms associated with CTHRC1 regulations, and opportunities and challenges regarding the development of CTHRC1 as a potential target for cancer management.

Expert Opinion: CTHRC1 is a multifaceted protein with critical roles in cancer progression and other pathological conditions. Its association with lower overall survival in various cancers, and impact on the tumor immune microenvironment make it an intriguing target for further research and potential therapeutic interventions in cancer.

Citing Articles

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References

Wong H, Sheng Q, Hesterberg A, Croessmann S, Rios B, Giri K . Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease. Nat Commun. 2022; 13(1):6036. PMC: 9562361. DOI: 10.1038/s41467-022-33780-1. View

Tameda M, Sugimoto K, Shiraki K, Yamamoto N, Okamoto R, Usui M . Collagen triple helix repeat containing 1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation and motility. Int J Oncol. 2014; 45(2):541-8. PMC: 4091966. DOI: 10.3892/ijo.2014.2445. View

Park E, Kim S, Jo J, Kim S, Hwang Y, Kim J . Collagen triple helix repeat containing-1 promotes pancreatic cancer progression by regulating migration and adhesion of tumor cells. Carcinogenesis. 2012; 34(3):694-702. DOI: 10.1093/carcin/bgs378. View

Mei P, Bai J, Miao F, Chen C, Zhu Y, Li Z . CTHRC1 mediates multiple pathways regulating cell invasion, migration and adhesion in glioma. Int J Clin Exp Pathol. 2020; 10(9):9318-9329. PMC: 6965956. View

Li Y, Fu Y, Gao Y, Li H, Ma L, Shu C . microRNA-134 inhibits melanoma growth and metastasis by negatively regulating collagen triple helix repeat containing-1 (CTHRC1). Int J Clin Exp Pathol. 2020; 11(9):4319-4330. PMC: 6962948. View

Chen G, Wang D, Zhao X, Cao J, Zhao Y, Wang F . miR-155-5p modulates malignant behaviors of hepatocellular carcinoma by directly targeting CTHRC1 and indirectly regulating GSK-3β-involved Wnt/β-catenin signaling. Cancer Cell Int. 2017; 17:118. PMC: 5721693. DOI: 10.1186/s12935-017-0469-8. View

Zhang W, Liu S, Zhan H, Yan Z, Zhang G . Transcriptome sequencing identifies key pathways and genes involved in gastric adenocarcinoma. Mol Med Rep. 2018; 18(4):3673-3682. PMC: 6131596. DOI: 10.3892/mmr.2018.9370. View

Li J, Cao J, Li M, Yu Y, Yang Y, Xiao X . Collagen triple helix repeat containing-1 inhibits transforming growth factor-b1-induced collagen type I expression in keloid. Br J Dermatol. 2011; 164(5):1030-6. DOI: 10.1111/j.1365-2133.2011.10215.x. View

Tang Z, Ding X, Qin S, Zhang C . [Effects of RNA interference of CTHRC1 on proliferation and apoptosis of thyroid papillary cancer TCP-1 cells ]. Nan Fang Yi Ke Da Xue Xue Bao. 2021; 41(4):549-554. PMC: 8110456. DOI: 10.12122/j.issn.1673-4254.2021.04.10. View

10.

Chen Y, Jia L, Zhao K, Chen Z, Han Y, He X . CTHRC1 promotes anaplastic thyroid cancer progression by upregulating the proliferation, migration, and invasion of tumor cells. PeerJ. 2023; 11:e15458. PMC: 10234271. DOI: 10.7717/peerj.15458. View

11.

Hu X, Bian Y, Wen X, Wang M, Li Y, Wan X . Collagen triple helix repeat containing 1 promotes endometrial cancer cell migration by activating the focal adhesion kinase signaling pathway. Exp Ther Med. 2020; 20(2):1405-1414. PMC: 7388291. DOI: 10.3892/etm.2020.8833. View

12.

Zhang X, Hu L, Yang Q, Qin W, Wang X, Xu C . CTHRC1 promotes liver metastasis by reshaping infiltrated macrophages through physical interactions with TGF-β receptors in colorectal cancer. Oncogene. 2021; 40(23):3959-3973. DOI: 10.1038/s41388-021-01827-0. View

13.

Ni S, Ren F, Xu M, Tan C, Weng W, Huang Z . CTHRC1 overexpression predicts poor survival and enhances epithelial-mesenchymal transition in colorectal cancer. Cancer Med. 2018; 7(11):5643-5654. PMC: 6247052. DOI: 10.1002/cam4.1807. View

14.

Liu Y, Du J, Li J, Tan X, Zhang Q . CTHRC1, a novel gene with multiple functions in physiology, disease and solid tumors (Review). Oncol Lett. 2023; 25(6):266. PMC: 10193374. DOI: 10.3892/ol.2023.13852. View

15.

Orloff M, Peterson C, He X, Ganapathi S, Heald B, Yang Y . Germline mutations in MSR1, ASCC1, and CTHRC1 in patients with Barrett esophagus and esophageal adenocarcinoma. JAMA. 2011; 306(4):410-9. PMC: 3574553. DOI: 10.1001/jama.2011.1029. View

16.

Han S, Zhu W, Yang W, Guan Q, Chen C, He Q . A Prognostic Signature Constructed by and in Stomach Adenocarcinoma. Front Genet. 2021; 12:646818. PMC: 8427509. DOI: 10.3389/fgene.2021.646818. View

17.

Yang J, Liu K, Yang L, Ji J, Qin J, Deng H . Identification and validation of a novel cuproptosis-related stemness signature to predict prognosis and immune landscape in lung adenocarcinoma by integrating single-cell and bulk RNA-sequencing. Front Immunol. 2023; 14:1174762. PMC: 10242006. DOI: 10.3389/fimmu.2023.1174762. View

18.

Kim H, Kim Y, Oh H, Kim K, Oh S, Kim J . Collagen triple helix repeat containing 1 (CTHRC1) acts via ERK-dependent induction of MMP9 to promote invasion of colorectal cancer cells. Oncotarget. 2014; 5(2):519-29. PMC: 3964226. DOI: 10.18632/oncotarget.1714. View

19.

Zhang K, Yue B, Duan X, Chen W, Dai X, Chen Y . Joint analysis identified FAP as a prognostic and diagnostic biomarker correlated immune infiltration in gastric cancer. Pathol Res Pract. 2023; 245:154462. DOI: 10.1016/j.prp.2023.154462. View

20.

Jiang F, Chen Y, Ren S, Li Z, Sun K, Xing Y . Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway. Int J Oncol. 2020; 57(1):183-196. PMC: 7252468. DOI: 10.3892/ijo.2020.5038. View