# The Emerging Role of CKAP4 in GI Cancer: From Molecular Pathways to Clinical Applications

## TL;DR

CKAP4 is a key protein in gastrointestinal cancers that promotes tumor growth and could serve as a new diagnostic and therapeutic target.

## Contribution

This review presents CKAP4 as a novel biomarker and therapeutic target in GI cancers, highlighting its diverse roles and mechanisms.

## Key findings

- CKAP4 interacts with DKK1 to activate the PI3K/AKT pathway, promoting cancer progression.
- CKAP4 shows potential as a serum biomarker for early detection and prognosis in multiple GI cancers.
- Targeting CKAP4 with antibodies or aptamers may offer new therapeutic strategies in GI malignancies.

## Abstract

CKAP4, originally identified as an endoplasmic reticulum protein, has been found to localize on the plasma membrane and function as a receptor for various ligands, notably Dickkopf-1 (DKK1). The interaction between DKK1 and CKAP4 activates the PI3K/AKT signaling pathway, promoting cancer cell proliferation and metastasis in various GI malignancies, including esophageal, gastric, pancreatic, and colorectal cancers. The review highlights new findings on CKAP4′s involvement in tumor progression, its potential as a diagnostic biomarker, and its promise as a therapeutic target. These findings could influence future studies by directing research towards developing CKAP4-targeted therapies, exploring its potential as a serum biomarker for early cancer detection, and investigating combination therapies that include CKAP4 inhibition.

Cytoskeleton-associated protein 4 (CKAP4) has emerged as a critical player in gastrointestinal (GI) cancer progression, diagnosis, and therapy. This comprehensive review synthesizes current knowledge on CKAP4′s multifaceted roles across GI malignancies, providing novel insights into its mechanisms of action and clinical potential. Its interaction with DKK1 and subsequent activation of the PI3K/AKT pathway underscores its role in promoting tumor growth. This review also highlights novel insights into CKAP4′s mechanisms of action beyond the well-established DKK1-CKAP4 axis, including its interaction with integrin β1 and involvement in angiogenesis through the FMNL2/EGFL6/CKAP4/ERK pathway. CKAP4′s impact on tumor microenvironment and immune evasion is elucidated, offering a new perspective on its contribution to cancer progression. In addition, CKAP4 arises as a promising serum biomarker for early detection and prognosis across multiple GI cancers, emphasizing its potential superiority over traditional markers. The therapeutic potential of targeting CKAP4 is extensively explored, including novel approaches like anti-CKAP4 antibodies and aptamers, and their synergistic effects with existing treatments. By integrating findings from esophageal, gastric, pancreatic, and colorectal cancers, this review provides a unique, comprehensive overview of CKAP4 in GI oncology, underscoring CKAP4′s potential to revolutionize GI cancer diagnosis and treatment and paving the way for future translational research.