Carcinoembryonic antigen-related cell adhesion molecule 1 in cancer - Blessing or curse?

Sep 21, 2026

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, also CD66a) is a transmembrane glycoprotein that mediates multiple physiological and pathological processes, including cancer. Clinical studies report contradictory functions regarding tumorigenicity. This narrative review clarifies CEACAM1’s clinical relevance across cancer entities, emphasizing tumor formation, progression, metastasis, and CEACAM1-driven treatment resistance. It also covers roles in cancer immunity, inflammatory microenvironment modulation, and therapeutic regimens targeting CEACAM1.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

CEACAM1 protein structure and function

Alternative splicing and isoforms

Ligand binding and signalling mechanisms

DOI: 10. 1111/eci.14337 NARRATIVE REVIEW Carcinoembryonic antigen-related cell adhesion molecule 1 in cancer: Blessing or curse? Lisa Götz1 | Uwe Rueckschloss1 | Sonia M. Najjar2 | Süleyman Ergün1 | Florian Kleefeldt1 1Institute of Anatomy and Cell Biology, University ofWuerzburg, Wuerzburg, Germany 2Department of Biomedical Sciences, Heritage College of Osteopathic Medicine Irvine Hall, Ohio University, Athens, Ohio, USA Correspondence Florian Kleefeldt, Institute of Anatomy and Cell Biology, University of Wuerzburg, Wuerzburg, Germany. Email: florian.kleefeldt@uni[wuerzburg.de](wuerzburg.de) Funding information Open Access Publication Fund of the University ofWürzburg; Cancer Research Advancement Foundation; Walter Schulz Foundation Abstract The Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, also CD66a), a transmembrane glycoprotein of the immunoglobulin superfamily, is a pivotal mediator of various physiological and pathological processes, including oncologic disorders. However, its precise role in tumorigenicity is contradictory discussed by several clinical studies. This review aims to elucidate the clinical significance ofCEACAM1 in different cancer entities focusing on tumour formation, progression and metastasis as well as on CEACAM1-mediated treatment resistance. Furthermore, we discuss the contribution of CEACAM1 to cancer immunity and modulation of the inflammatory microenvironment and finally provide a comprehensive review of treatment regimens targeting this molecule. KEYWORDS cancer, CD66a, CEACAM1, inflammation, tumorigenicity, tumour microenvironment 1 | CEACAM1 PROTEIN STRUCTURE AND FUNCTION The Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), also known as cluster of differentiation 66a (CD66a), was first discovered as a biliary glycoprotein of hepatocytes1 and was later found to be ubiquitously expressed in various other tissues and cells, including immune,2 endothelial,3 and cancer cells.4 As a member of CEA-related cell adhesion molecules belonging to the immunoglobulin superfamily, CEACAM1 exerts tissue-specific biological functions by mediating homophilic and heterophilic ligand binding.5–7 Additionally, CEACAM1 can serve as a co-receptor modulating the downstream signalling of its targeted receptor protein.5,8 Furthermore, it can act as a receptor for certain pathogens, including bacteria and viruses, thereby playing a role in infection and host defence mechanisms.9–11 Due to alternative splicing, human CEACAM1 is expressed as 12 different isoforms, which differ fundamentally in their protein structure (Figure 1) .12 The ectodomain of the single pass transmembrane protein consists of a substantial N-terminal IgV-related domain linked to up to three heavily glycosylated IgC2-domains.13,14 Depending on the inclusion or absence of CEACAM1 exon 7, the intracellular domain either exists in a long form (CEACAM1-L), harbouring two immunoreceptor tyrosine-based inhibitory motifs (ITIMs), or a short version (CEACAM1-S) without an ITIM motif, respectively.15 Besides, in three splice isoforms a premature stop codon leads to the exclusion of the transmembrane domain, resulting in soluble protein variants. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation. Eur J Clin Invest. 2024;54(Suppl. 2):e14337 . [https://doi.org/10.1111/eci.14337](https://doi.org/10.1111/eci.14337) [wileyonlinelibrary.com/journal/eci](wileyonlinelibrary.com/journal/eci) 1 of 12 FIGURE 1 Alternative splicing of human CEACAM1 yields 12 isoforms

FAQs

What is CEACAM1 and why is it important in cancer research?

CEACAM1 (also CD66a) is a transmembrane glycoprotein involved in key physiological and pathological processes, including oncologic disorders, with an emphasized but debated role in tumorigenicity.

How do different CEACAM1 isoforms arise, and what does that change?

Alternative splicing generates 12 CEACAM1 isoforms with distinct protein structures, including long (CEACAM1-L) and short (CEACAM1-S) forms that differ in the presence of intracellular ITIM motifs, as well as soluble variants lacking transmembrane and cytoplasmic domains.

How does CEACAM1-L signalling work?

CEACAM1-L downstream signalling relies on intracellular ITIM motifs that recruit signalling molecules such as SRC family kinases and cytoplasmic tyrosine phosphatases via SH2-domain interactions, producing activating or inhibitory effects depending on isoform expression ratios.

Sep 21, 2026

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