The role of collagen triple helix repeat containing 1 (CTHRC1) in cancer development and progression

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.

KEYWORDS:

• CTHRC1
• cancer
• cancer-associated signaling
• cancer immune signaling
• tumor immune microenvironment
• ingenuity pathway analysis (IPA)

Article highlights

• This article reviews the role of CTHRC1 in various cancers and its associations with clinicopathologies, cancer-related processes, and cancer-associated signaling molecules.

• CTHRC1 is consistently overexpressed in various cancers, promoting tumor growth and metastasis, and leading to poor prognosis.

• There are currently no inhibitors that specifically target CTHRC1. Future research should focus on finding an effective CTHRC1 inhibitor.

• CTHRC1 plays a crucial role in tumor microenvironment by regulating immune cell infiltration, immune signaling, and immunosuppressive and oncogenic factors. This makes it a promising sub-target with immunotherapy for improved treatment outcomes.

• CTHRC1 overexpression is also associated with non-cancerous conditions, including rheumatoid arthritis, myelination issues, and keloid scarring. Its diagnostic and prognostic values should be carefully evaluated.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was partially supported by funding from the NIH [R01CA261937] and the Department of Veterans Affairs (Merit Review Awards; BLR&D I01BX005917; CSR&D I01CX002210; and a Senior Research Career Scientist Award BLR&D IK6BX006041 to NA). This study was also supported by the University of Wisconsin Foundation’s Dr. Frederic E. Mohs Skin Cancer Research Chair endowment to N Ahmad.