Towards understanding the mechanisms of actions of CEACAM6 in cancer progression

Abstract

Human carcinoembryonic antigen (CEA) is the prototypic member of highly related cell surface glycoproteins that includes Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) and others. CEACAM6 (formerly NCA) that belongs to the immunoglobulin superfamily, is a cell adhesion proteins of the CEA family. It is normally expressed on the epithelial surfaces and the surface of myeloid (CD66c). CEACAM6 is a multi-functional glycoprotein that mediates homotypic binding with other CEA family members and heterotypic binding with integrin receptors. It functions by organizing tissue architecture and regulating different signal transduction, while aberrant expression leads to the development of human malignancies. It was firstly discovered in proliferating cells of adenomas and hyperplastic polyps in comparison to benign colonic tissue when over-expressed on the surface of various cell types in model systems. CEACAM6, functions as a pan-inhibitor of cell differentiation and cell polarization, and it also cause distortion of tissue architecture. Moreover, over-expression of CEACAM6 modulates cancer progression through aberrant cell differentiation, anti-apoptosis, cell growth and resistance to therapeutic agents. In addition, CEACAM6 over-expression in multiple malignancies promoting cell invasion and metastasis thereby representing an acquired advantage of tumor cells directly responsible for an invasive phenotype. This review will focus on the findings supporting the mechanism of actions linking the oncogenic potential of CEACAM6 to the onset of cancer progression and pathogenesis specially in breast cancer, and to validate CEACAM6 as a target to pave the way towards the design of efficient therapeutic strategies against BC.

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