GPI-anchored CEA family glycoproteins CEA and CEACAM6 mediate their biological effects through enhanced integrin alpha5beta1-fibronectin interaction
- PMID: 17167768
- DOI: 10.1002/jcp.20887
GPI-anchored CEA family glycoproteins CEA and CEACAM6 mediate their biological effects through enhanced integrin alpha5beta1-fibronectin interaction
Abstract
Carcinoembryonic antigen (CEA) and CEA family member CEACAM6 are glycophosphatidyl inositol (GPI)-anchored, intercellular adhesion molecules that are up-regulated in a wide variety of human cancers, including colon, breast, and lung. When over-expressed in a number of cellular systems, these molecules are capable of inhibiting cellular differentiation and anoikis, as well as disrupting cell polarization and tissue architecture, thus increasing tumorigenicity. The present study shows that perturbation of the major fibronectin receptor, integrin alpha5beta1, underlies some of these biological effects. Using confocal microscopy and specific antibodies, CEA and CEACAM6 were demonstrated to co-cluster with integrin alpha5beta1 on the cell surface. The presence of CEA and CEACAM6 was shown to lead to an increase in the binding of the integrin alpha5beta1 receptor to its ligand fibronectin, without changing its cell surface levels, resulting in increased adhesion of CEA/CEACAM6-expressing cells to fibronectin. More tenacious binding of free fibronectin to cells led to enhanced fibronectin matrix assembly and the formation of a polymerized fibronectin "cocoon" around the cells. Disruption of this process with specific monoclonal antibodies against either fibronectin or integrin alpha5beta1 led to the restoration of cellular differentiation and anoikis in CEA/CEACAM6 producing cells.
Copyright 2006 Wiley-Liss, Inc.
Similar articles
-
A co-clustering model involving alpha5beta1 integrin for the biological effects of GPI-anchored human carcinoembryonic antigen (CEA).J Cell Physiol. 2007 Jun;211(3):791-802. doi: 10.1002/jcp.20989. J Cell Physiol. 2007. PMID: 17286276
-
Fibronectin fibrillogenesis, a cell-mediated matrix assembly process.Matrix Biol. 2005 Sep;24(6):389-99. doi: 10.1016/j.matbio.2005.06.008. Matrix Biol. 2005. PMID: 16061370 Review.
-
c-Src-dependent cross-talk between CEACAM6 and alphavbeta3 integrin enhances pancreatic adenocarcinoma cell adhesion to extracellular matrix components.Biochem Biophys Res Commun. 2004 Apr 23;317(1):133-41. doi: 10.1016/j.bbrc.2004.03.018. Biochem Biophys Res Commun. 2004. PMID: 15047158
-
[CEACAM1--a less well-known member of the family of carcinoembryonic antigens].Cas Lek Cesk. 2003;142(5):259-63. Cas Lek Cesk. 2003. PMID: 12920788 Review. Czech.
-
Human carcinoembryonic antigen functions as a general inhibitor of anoikis.Cancer Res. 2000 Jul 1;60(13):3419-24. Cancer Res. 2000. PMID: 10910050
Cited by
-
The emerging roles of CEACAM6 in human cancer (Review).Int J Oncol. 2024 Mar;64(3):27. doi: 10.3892/ijo.2024.5615. Epub 2024 Jan 19. Int J Oncol. 2024. PMID: 38240103 Free PMC article. Review.
-
Anoikis resistance--protagonists of breast cancer cells survive and metastasize after ECM detachment.Cell Commun Signal. 2023 Aug 3;21(1):190. doi: 10.1186/s12964-023-01183-4. Cell Commun Signal. 2023. PMID: 37537585 Free PMC article. Review.
-
Generation and in vivo characterization of a novel high-affinity human antibody targeting carcinoembryonic antigen.MAbs. 2023 Jan-Dec;15(1):2217964. doi: 10.1080/19420862.2023.2217964. MAbs. 2023. PMID: 37243574 Free PMC article.
-
Anoikis-Associated Lung Cancer Metastasis: Mechanisms and Therapies.Cancers (Basel). 2022 Sep 30;14(19):4791. doi: 10.3390/cancers14194791. Cancers (Basel). 2022. PMID: 36230714 Free PMC article. Review.
-
CEACAM6 serves as a biomarker for leptomeningeal metastasis in lung adenocarcinoma.Cancer Med. 2023 Feb;12(4):4521-4529. doi: 10.1002/cam4.5221. Epub 2022 Sep 9. Cancer Med. 2023. PMID: 36082960 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources