CEACAM6

What is CEACAM6 protein?

CEACAM6 gene (CEA cell adhesion molecule 6) is a protein coding gene which situated on the long arm of chromosome 19 at locus 19q13. This gene encodes a protein that belongs to the carcinoembryonic antigen (CEA) family whose members are glycosyl phosphatidyl inositol (GPI) anchored cell surface glycoproteins. Members of this family play a role in cell adhesion and are widely used as tumor markers in serum immunoassay determinations of carcinoma. This gene affects the sensitivity of tumor cells to adenovirus infection. The CEACAM6 protein is consisted of 344 amino acids and CEACAM6 molecular weight is approximately 37.2 kDa.

What is the function of CEACAM6 protein?

CEACAM6 is a cell adhesion molecule belonging to the CEA family. It plays an important role in a variety of cancers, including promoting tumor proliferation, invasion, and metastasis. CEACAM6 is usually upregulated in a variety of cancers, including pancreatic, breast, non-small cell lung, gastric, and colorectal cancers, and is associated with poor prognosis. It promotes tumor cell proliferation, invasion, migration, resistance to apoptosis and chemotherapy, and angiogenesis by activating downstream signaling pathways such as ERK1/2/MAPK or SRC/FAK/PI3K/AKT, directly or through EGFR. In addition, CEACAM6 expression is regulated by a variety of factors, including the CD151/TGF-β1/Smad3 axis, multiple micrornas (such as miR-146, miR-26a, miR-29a/b/c, etc.), and DNA methylation. In terms of clinical applications, CEACAM6 is a potential diagnostic biomarker and therapeutic target, and monoclonal antibodies and molecular therapeutic strategies targeting CEACAM6 are being developed for the diagnosis and treatment of cancer.

CEACAM6 related signaling pathway

CEACAM6 is a cell surface molecule that plays a role in a variety of biological processes, including cell adhesion, signaling, and cell migration. In cancer, CEACAM6 promotes tumor invasion and metastasis by interacting with multiple signaling pathways. It can activate signaling pathways such as PI3K/AKT and ERK/MAPK, thereby promoting epithelial-mesenchymal transformation (EMT) and increasing the migration and invasion ability of tumor cells. In addition, CEACAM6 is involved in the regulation of tumor angiogenesis and immune responses in the tumor microenvironment. Clinically, CEACAM6 expression levels are associated with the prognosis of a variety of cancers, making it a potential diagnostic marker and therapeutic target.

Fig1. Signaling initiated by epithelial CEACAMs. (Arnaud Kengmo Tchoupa, 2014)

CEACAM6 related diseases

CEACAM6 plays an important role in a variety of cancers, including pancreatic, lung, stomach, colorectal, breast, cholangiocarcinoma, ovarian, head and neck cancer, osteosarcoma, acute leukemia, and urinary system tumors. It is commonly upregulated in these cancers and is associated with tumor aggressiveness, metastasis, drug resistance, and poor prognosis. CEACAM6 promotes the proliferation, migration and invasion of tumor cells by activating various signaling pathways, such as PI3K/AKT, ERK/MAPK, etc. In addition, CEACAM6 expression is regulated by multiple factors, including miRNA, DNA methylation, and protein glycosylation. Clinically, high expression of CEACAM6 is associated with poor prognosis in a variety of cancers, making it a potential diagnostic and therapeutic target.

Bioapplications of CEACAM6

CEACAM6 plays a catalytic role in a variety of cancers, including pancreatic, stomach, lung, colorectal, and more. It plays a key role in tumor occurrence and development by promoting tumor invasion, metastasis and angiogenesis, inhibiting tumor apoptosis, and increasing tumor resistance to chemotherapy drugs. High expression of CEACAM6 is often associated with poor patient outcomes. Therapeutic strategies targeting CEACAM6, such as the development of specific antibodies, have been shown to inhibit tumor invasion and metastasis and increase the sensitivity of tumor cells to apoptosis, providing new research directions for early diagnosis and treatment of cancer. In addition, CEACAM6 also plays an important role in modulating the immune response in the tumor microenvironment, and its potential in cancer therapy is gradually being explored, including as a target for cancer therapy and as a component of immunotherapy.

Case Study 1: Shah Kamranur Rahman, 2021

Influenza A virus (IAV) enters human lung cells by binding to the host glycoprotein CD66c, a receptor not previously identified. This study demonstrates that IAV's neuraminidase protein interacts with CD66c on the cell surface, and increasing CD66c levels enhances viral entry. CD66c's binding capacity surpasses that of other glycoproteins like EGFR and DC-SIGN, which are known to aid IAV entry. Reducing CD66c with siRNA or blocking it with antibodies inhibits viral binding and entry. CD66c specificity for IAV is confirmed by its lack of impact on Hepatitis C virus entry. Moreover, pre-incubating IAV with recombinant CD66c protein and administering it intranasally in mice reduces lung cytopathic effects, suggesting CD66c's role in IAV infection.

Fig1. Lec2 CHO-CD66c is CD66c overexpressing Lec2 CHO cell lines.

Fig2. siRNA knockdown of CD66c in Huh7.5 cells have not inhibited entry of another non-IAV virus.

Case Study 2: Jacqueline I Keenan, 2014

Exclusive enteral nutrition (EEN) is a recognized first-line treatment for inducing remission in active Crohn's disease (CD), particularly in pediatric patients, yet the specific mechanisms behind its efficacy are not completely understood. This study utilized the Caco-2 human adenocarcinoma cell line to demonstrate that exposure to a polymeric formula (PF), a form of EEN, leads to a dose-dependent upregulation of CEACAM6, an adhesion molecule that plays a role in CD pathogenesis by facilitating the binding of adherent-invasive Escherichia coli (AIEC) to the intestinal lining. Notably, the increase in CEACAM6 expression was most pronounced on the cell surface. Additionally, PF treatment doubled the secretion of soluble CEACAM6 by Caco-2 cells, and this elevated release was associated with a reduced capacity of AIEC to adhere to intestinal epithelial cells.

Fig3. Detection of CEACAM6 in a Caco-2 cell lysate.

Fig4. PF added to Caco-2 cells for 24 h had a dose-dependent effect on CEACAM6 expression.

CEACAM6 has several biochemical functions, for example, protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by CEACAM6 itself. We selected most functions CEACAM6 had, and list some proteins which have the same functions with CEACAM6. You can find most of the proteins on our site.

CEACAM6 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with CEACAM6 here. Most of them are supplied by our site. Hope this information will be useful for your research of CEACAM6.

CARTPT;CEACAM5;CEACAM1;CEACAM8;CEACAM7