CEACAM6 - CEA cell adhesion molecule 6 |Elisa - Clia - Antibody - Protein

Background

CEACAM6, also known as CD66c (Cluster of Differentiation 66c), is a member of the carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), which belong to the larger immunoglobulin superfamily (IgSF). CEACAM6 is a glycoprotein primarily involved in intercellular adhesion, immune response modulation, and tumor progression. It is expressed on the surface of various cell types, particularly epithelial cells, granulocytes, and certain cancer cells. CEACAM6, like other CEACAM family members, plays a key role in cellular interactions and communication.

In addition to its normal physiological roles in cell adhesion, CEACAM6 is implicated in tumorigenesis, especially in cancers like colorectal, pancreatic, lung, and breast cancer. CEACAM6 is often overexpressed in these malignancies, contributing to tumor growth, metastasis, and resistance to apoptosis. Its expression in the immune system and epithelial cells also means it has important functions in immune modulation and maintaining the integrity of epithelial barriers.

Protein Structure

CEACAM6 is a glycosylated membrane protein and shares many structural features with other members of the CEACAM family. The structure of CEACAM6 is essential for its role in mediating cell-cell adhesion and immune modulation.

Extracellular Domain:

The extracellular portion of CEACAM6 consists of three immunoglobulin (Ig)-like domains:

• One N-terminal Ig variable (IgV)-like domain: This domain mediates homophilic (self-self) and heterophilic (self-other) interactions, allowing CEACAM6 to interact with itself or with other CEACAM family members. This domain is critical for the protein's adhesion functions.
• Two Ig constant (IgC)-like domains: These are involved in the structural stability of the protein and assist in binding interactions with other molecules, including those in the immune system and the extracellular matrix.
• Glycosylation: The extracellular domain of CEACAM6 is heavily N-glycosylated, with several glycosylation sites. This glycosylation impacts the protein's adhesion properties, structural stability, and interactions with other proteins. The glycosylation also plays a role in how CEACAM6 interacts with pathogens, such as bacteria.

Transmembrane Domain:

• CEACAM6 has a glycosylphosphatidylinositol (GPI) anchor instead of a typical transmembrane domain. The GPI anchor attaches the protein to the cell membrane through lipid interactions rather than spanning the membrane itself. This feature allows CEACAM6 to be highly mobile within the membrane, facilitating its role in cell signaling and adhesion.

Cytoplasmic Domain:

• CEACAM6 does not have a conventional intracellular domain because it is anchored to the membrane via a GPI linkage. As a result, it lacks the cytoplasmic signaling motifs present in other transmembrane proteins. However, CEACAM6 still participates in signaling pathways indirectly by interacting with other receptors or proteins on the cell surface.

Classification and Subtypes

CEACAM6 is classified within the carcinoembryonic antigen (CEA) family, which is part of the larger immunoglobulin superfamily (IgSF). The CEA family includes several members such as CEACAM1, CEACAM5 (CEA), and CEACAM8, all of which are involved in cell-cell adhesion and immune regulation.

Unlike CEACAM1, which is widely expressed in many tissues, CEACAM6 has a more restricted pattern of expression, being prominent on epithelial cells, granulocytes, and certain cancer cells. CEACAM6 is primarily studied in its context of overexpression in various cancers, where it plays a role in tumor progression.

CEACAM6 does not have subtypes per se, but its expression levels and functional roles may vary depending on the tissue type and disease state. For example, its overexpression in tumors often correlates with poor prognosis and aggressive tumor behavior.

Function and Biological Significance

CEACAM6 has several important roles in both normal cellular physiology and pathological conditions, particularly in immune responses, cell adhesion, and cancer progression.

Cell Adhesion:

• CEACAM6 mediates homophilic (binding to itself) and heterophilic (binding to other molecules) cell-cell adhesion, particularly between epithelial cells. It helps maintain tissue architecture and facilitates interactions between cells in various tissues.
• In epithelial tissues, CEACAM6 contributes to the integrity of the epithelial barrier, which is crucial for protecting against pathogen invasion and maintaining tissue homeostasis.

Immune Regulation:

• CEACAM6 is involved in modulating immune responses, particularly those involving neutrophils and other granulocytes. It is expressed on the surface of activated neutrophils and plays a role in the immune response to infections, particularly bacterial infections.
• CEACAM6 can also interact with pathogens. For example, certain bacteria, such as Neisseria gonorrhoeae and Helicobacter pylori, can bind to CEACAM6 on host cells, facilitating bacterial adhesion and immune evasion. This interaction underscores CEACAM6's role in the host-pathogen interface.

Tumorigenesis and Cancer Progression:

• CEACAM6 is overexpressed in many cancers, including colorectal, pancreatic, lung, and breast cancers. In these cancers, CEACAM6 promotes tumor cell adhesion, invasion, and metastasis by facilitating interactions with the extracellular matrix and other cells.
• CEACAM6 also plays a role in apoptosis resistance, particularly in cancer cells. Its overexpression can inhibit programmed cell death, contributing to tumor survival and growth. This anti-apoptotic effect is particularly important in chemotherapy resistance, where cancer cells evade treatment-induced death.
• CEACAM6 can interact with integrins and other adhesion molecules on cancer cells, enhancing their ability to invade surrounding tissues and migrate to distant organs, promoting metastasis.

Pathogen Interactions:

• CEACAM6 serves as a receptor for certain bacteria, such as Escherichia coli, Neisseria species, and Helicobacter pylori, allowing these pathogens to adhere to host cells. This interaction can lead to immune evasion by the pathogens and facilitate infection.

Clinical Issues

Cancer Diagnosis and Prognosis:

• CEACAM6 is widely used as a biomarker in various cancers due to its overexpression in tumor cells. Elevated levels of CEACAM6 are often correlated with poor prognosis, increased tumor aggressiveness, and chemotherapy resistance. For example, in pancreatic cancer, CEACAM6 is a key marker of tumor invasiveness and is associated with shorter patient survival times.
• Monitoring CEACAM6 expression can help in diagnosing certain cancers and assessing the likelihood of tumor recurrence or metastasis. It is used as part of panels to evaluate tumor progression and response to therapy.

Therapeutic Targeting:

• Given its role in tumor progression and apoptosis resistance, CEACAM6 has been explored as a therapeutic target in cancer treatment. Inhibiting CEACAM6 expression or function could potentially reduce tumor growth and enhance the effectiveness of existing treatments, such as chemotherapy and targeted therapies.
• CEACAM6-targeted therapies, such as monoclonal antibodies, are being investigated to block its function in tumor cells, aiming to reduce adhesion, invasion, and survival in metastatic cancer cells.

Bacterial Infections:

• CEACAM6’s role as a bacterial receptor suggests it could be a target for therapies aimed at preventing pathogen adhesion to host cells. By blocking the interaction between bacteria and CEACAM6, it may be possible to reduce bacterial colonization and infection, particularly in diseases caused by Neisseria and Helicobacter.

Inflammatory Diseases:

• CEACAM6 is also implicated in inflammatory diseases where neutrophil activation plays a key role. In conditions such as inflammatory bowel disease (IBD) and chronic obstructive pulmonary disease (COPD), CEACAM6 may contribute to neutrophil recruitment and activation, exacerbating tissue damage and inflammation.

Summary

CEACAM6 (CD66c) is a glycoprotein in the carcinoembryonic antigen (CEA) family, primarily involved in cell-cell adhesion and immune regulation. Structurally, it contains three Ig-like domains and is anchored to the cell membrane by a GPI anchor, allowing it to interact dynamically with other cells and molecules. CEACAM6 plays a significant role in immune responses, epithelial integrity, and tumor progression. It is overexpressed in several types of cancer, where it promotes tumor growth, metastasis, and resistance to apoptosis.

Clinically, CEACAM6 serves as an important biomarker for cancer diagnosis and prognosis and is being explored as a therapeutic target in oncology. Its role in bacterial infections and inflammatory diseases further underscores its significance in both health and disease. Targeting CEACAM6 through therapeutic strategies holds promise in reducing tumor aggressiveness and improving treatment outcomes in cancers where it is overexpressed.