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Exploring the interactions of integrins and CEACAM6 (Review)

  • Authors:
    • Aisha Al‑Khinji
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    Affiliations: College of Medicine, Qatar University, P.O. Box 2713, Doha, Qatar
    Copyright: © Al‑Khinji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 237
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    Published online on: September 29, 2025
       https://doi.org/10.3892/etm.2025.12986
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancer types, and is characterized by rapid progression, resistance to therapy and poor overall prognosis. Adhesion molecules can influence signal transduction, survival, pathogenesis, development and progression in PDAC. However, the role of adhesion molecules and therapeutic targets in PDAC is inadequately characterized. Therefore, the present review critically evaluated the interactions, associations and co‑expression patterns of adhesion molecules in PDAC. The interaction between adhesion molecules, such as carcinoembryonic antigen‑related cell adhesion molecules (CEACAMs) and integrins, can influence the differentiation, activation, proliferation, metastasis and cytoskeletal remodeling of cancer cells. In addition, adhesion molecules can regulate tumor progression, metastasis, and cellular adhesion and signaling. The present analysis has brought to attention the interaction between CEACAM6 and integrins, which may affect the prognosis of PDAC. Functional and molecular evaluation revealed that CEACAM6 contributes to resistance to anoikis in PDAC through interactions with partner proteins and activation of survival signaling pathways, particularly the Src/focal adhesion kinase axis. In conclusion, the interaction between CEACAM6 and integrins can influence PDAC progression, desmoplasia and treatment resistance. Targeting this adhesion signaling axis presents a promising strategy to improve diagnostic precision and develop more effective personalized therapies for PDAC.
View Figures

Figure 1

Integrin and CEACAM adhesion
receptors in pancreatic ductal adenocarcinoma. (A) Integrin (left)
receptors with a cytoplasmic domain contain α and β subunits with
EGF-like and calcium-binding domains, which link to intracellular
signaling via talin and focal adhesion kinase (FAK), and (B)
CEACAMs with either a transmembrane receptor anchored by
glycosylphosphatidylinositol on the cell surface, such as CEACAM6
and CEACAM5, or (C) CEACAM receptors with a cytoplasmic domain,
such as CEACAM1 and CEACAM3. Talin is illustrated as a cytoskeletal
adaptor protein that connects integrins to the actin cytoskeleton
and, functionally, to CEACAM-associated signaling hubs. While
direct binding of CEACAMs to talin has not been fully demonstrated,
CEACAMs and integrins co-localize in lipid rafts, enabling shared
downstream signaling via Src/FAK and PI3K/Akt pathways. CEACAM,
carcinoembryonic antigen-related cell adhesion molecule; FAK, focal
adhesion kinase; RhoA, Ras homolog family member A; ROCK, Rho
associated protein kinase.

Figure 2

A selection of human CEACAM family
members showing different CEACAM structures. CEACAM5, CEACAM6,
CEACAM7, and CEACAM8 lack transmembrane and cytosolic domains,
while CEACAM1 is anchored through transmembrane domains. The blue
spheres represent constant domains depicted by A and B. The red
spheres are the variable N-terminal Ig variable-like domain.
CEACAM, carcinoembryonic antigen-related cell adhesion
molecule.

Figure 3

CEACAM6 involvement in six of the
cancer hallmarks. CEACAM6 has multiple mechanisms in pancreatic
ductal adenocarcinoma and contributes to these biological
processes. CEACAM6 sustains proliferation through PI3K/Akt pathways
and induces angiogenesis via MMP-9. However, the involvement of
CEACAM6 in replicative immortality is inconclusive. CEACAM,
carcinoembryonic antigen-related cell adhesion molecule.

Figure 4

STRING protein-protein network
analysis of the relationship between CEACAM6 and integrins. The
network was generated using the STRING database (v11.5; https://string-db.org). Lines represent known or
predicted associations with the following sources: Curated
databases (light blue), experimentally determined (pink), gene
neighborhood (green), gene fusions (red), gene co-occurrence
(blue), text mining (yellow), co-expression (black) and protein
homology (lavender) CEACAM, carcinoembryonic antigen-related cell
adhesion molecule; ITG, integrin.
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Copy and paste a formatted citation
Spandidos Publications style
Al‑Khinji A: Exploring the interactions of integrins and CEACAM6 (Review). Exp Ther Med 30: 237, 2025.
APA
Al‑Khinji, A. (2025). Exploring the interactions of integrins and CEACAM6 (Review). Experimental and Therapeutic Medicine, 30, 237. https://doi.org/10.3892/etm.2025.12986
MLA
Al‑Khinji, A."Exploring the interactions of integrins and CEACAM6 (Review)". Experimental and Therapeutic Medicine 30.6 (2025): 237.
Chicago
Al‑Khinji, A."Exploring the interactions of integrins and CEACAM6 (Review)". Experimental and Therapeutic Medicine 30, no. 6 (2025): 237. https://doi.org/10.3892/etm.2025.12986
Copy and paste a formatted citation
x
Spandidos Publications style
Al‑Khinji A: Exploring the interactions of integrins and CEACAM6 (Review). Exp Ther Med 30: 237, 2025.
APA
Al‑Khinji, A. (2025). Exploring the interactions of integrins and CEACAM6 (Review). Experimental and Therapeutic Medicine, 30, 237. https://doi.org/10.3892/etm.2025.12986
MLA
Al‑Khinji, A."Exploring the interactions of integrins and CEACAM6 (Review)". Experimental and Therapeutic Medicine 30.6 (2025): 237.
Chicago
Al‑Khinji, A."Exploring the interactions of integrins and CEACAM6 (Review)". Experimental and Therapeutic Medicine 30, no. 6 (2025): 237. https://doi.org/10.3892/etm.2025.12986
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