Carcinoembryonic antigen-related cell adhesion molecule 6, known as CEACAM6, is a protein found on the surface of cells. It belongs to a larger group of proteins called the carcinoembryonic antigen (CEA) family, which are anchored to the cell membrane. These proteins are involved in various cellular processes and are sometimes used as markers in the detection of certain cancers. CEACAM6 plays a part in connecting cells and transmitting signals within and between cells.
Normal Biological Roles
CEACAM6 is normally present on the surface of epithelial cells and some immune cells, such as granulocytes. In healthy tissues, CEACAM6 contributes to cell-to-cell adhesion, helping cells stick together and maintain the structure of tissues.
The protein also participates in cell signaling, which involves the communication pathways that regulate cell behavior. These signaling roles can influence processes like cell proliferation and differentiation. In the gut, CEACAM6 is expressed in intestinal epithelial cells and contributes to the integrity of the gut barrier, helping to regulate what passes through the intestinal lining.
Involvement in Cancer
CEACAM6 is frequently found at increased levels in various types of cancer. This overexpression has been observed in pancreatic, colorectal, lung, breast, gastric, and hepatocellular cancers. Higher levels of CEACAM6 are often linked to a less favorable outlook for patients, including shorter overall survival and disease-free survival.
The protein contributes to cancer progression by promoting the uncontrolled growth of tumor cells. It helps cancer cells resist programmed cell death, a process known as anoikis resistance. CEACAM6 also enhances the ability of cancer cells to invade surrounding tissues and spread to distant parts of the body, a process called metastasis.
CEACAM6’s involvement in cancer also extends to its role in promoting the formation of new blood vessels that feed tumors, a process called angiogenesis. It can also contribute to drug resistance, making some cancer treatments less effective. For example, in gastric cancer, increased CEACAM6 levels are associated with tumor size, lymph node metastasis, and distant metastasis, and can be inversely correlated with the five-year survival rate.
Other Disease Connections
Beyond cancer, CEACAM6 has connections to other diseases, particularly inflammatory conditions. It has been investigated for its role in Inflammatory Bowel Disease (IBD). In Crohn’s disease, CEACAM6 acts as a receptor for certain bacteria, specifically adherent-invasive E. coli (AIEC), supporting their colonization of the ileal mucosa.
Increased expression of CEACAM6 has been observed in the ileal mucosa of patients with Crohn’s disease, even in areas not directly affected by inflammation. This increased expression can be influenced by inflammatory cytokines, which might promote bacterial colonization. CEACAM6 has also been shown to act as a receptor for other pathogens, including Salmonella typhimurium and Neisseria species, and more recently, for the Influenza A virus, facilitating its entry into human lung cells.
Therapeutic Potential
Understanding the varied roles of CEACAM6 in disease has opened pathways for new therapeutic approaches. CEACAM6’s differential expression on the surface of tumor cells makes it a promising marker for diagnosing certain cancers. For instance, elevated CEACAM6 levels in serum have been detected in patients with gastric carcinoma and lung adenocarcinoma, potentially serving as a diagnostic biomarker.
CEACAM6 is also being explored as a target for drug development. Researchers are investigating strategies such as using antibodies to block its function or small molecules to inhibit its activity. This ongoing research aims to translate the understanding of CEACAM6’s biology into more precise and effective treatments for various diseases.