CEACAM5

Fig1. CEACAM interactions. (Jerin Thomas, 2023)

What is CEACAM5 protein?

CEACAM5 gene (CEA cell adhesion molecule 5) is a protein coding gene which situated on the long arm of chromosome 19 at locus 19q13. This gene encodes a cell surface glycoprotein that represents the founding member of the carcinoembryonic antigen (CEA) family of proteins. The encoded protein is used as a clinical biomarker for gastrointestinal cancers and may promote tumor development through its role as a cell adhesion molecule. Additionally, the encoded protein may regulate differentiation, apoptosis, and cell polarity. The CEACAM5 protein is consisted of 702 amino acids and CEACAM5 molecular weight is approximately 76.8 kDa.

What is the function of CEACAM5 protein?

CEACAM5, also known as CD66e or CEA, is a cell surface glycoprotein that belongs to the CEACAM family. It plays a role in a variety of biological processes, including cell adhesion, cell signaling, and tumor progression. CEACAM5 regulates intercellular interactions by homotypic and heterotypic binding with other CEACAM family members. In addition, CEACAM5 has a particularly important role in tumor biology, which may play a role by promoting tumor progression and inhibiting apoptosis. In clinical applications, CEACAM5 expression levels are used to monitor cancer progression and recurrence, as well as as a prognostic indicator for certain types of cancer. In addition, CEACAM5 is also being studied as a target for immunotherapy, particularly in CAR T cell therapy, where CAR T cells targeting CEACAM5 are being developed to treat certain types of cancer.

CEACAM5 related signaling pathway

CEACAM5 is a cell surface protein that belongs to the carcinoembryonic antigen family. When CEACAM5 aggregates on the cell surface, it can activate a variety of signaling pathways, the most common of which are the activation of Src kinase and FAK (plaque adhesion kinase). These signaling pathways can further influence a variety of biological processes within cells, including cell proliferation, cell migration, and cell survival. For example, CEACAM5 promotes cell cycle progression through activation of Src kinase, and enhances cell adhesion and migration through activation of FAK. In addition, CEACAM5 can further influence the biological behavior of cells by regulating other signaling pathways such as PI3K/AKT and MAPK.

CEACAM5 related diseases

CEACAM5 plays an important role in a variety of cancers. Its expression is limited in normal tissues, but upregulated in a variety of cancers, including cancers of the gastrointestinal tract, genitourinary system, respiratory system, and breast. High expression of CEACAM5 is closely associated with tumor invasiveness, metastasis, and prognosis, especially in colorectal cancer, gastric cancer, and non-small cell lung cancer. For example, in colorectal cancer, CEACAM5 expression is widely used as a prognostic marker. Abnormal expression of CEACAM5 is also associated with tumor proliferation, migration, and EMT processes, suggesting that it may promote epithelioid properties of tumor cells by affecting specific signaling pathways, thereby affecting tumor metastasis and growth. In addition, CEACAM5 also plays a role in the metastasis of breast cancer, and its expression level correlates with tumor aggressiveness and prognosis. In non-small cell lung cancer, CEACAM5 expression is significantly associated with tumor stage, lymphatic invasion, and histological grade, and its high expression may be associated with poorer prognosis.

Bioapplications of CEACAM5

CEACAM5 is highly expressed in a variety of epithelial tumors, and CEACAM5 has become a potential target for cancer therapy. Therapeutic strategies targeting CEACAM5 include antibody drug conjugators (ADCs), bisspecific antibodies, and CAR T cell therapy. CEACAM5 expression levels are also being studied as a biomarker to predict response to immunotherapy in patients with certain types of cancer. In terms of clinical development, researchers are fully developing CEACAM5 as a biologic therapy for multiple novel therapeutic targets, including monoclonal antibodies, ADCs, bisspecific antibodies and CAR-T therapies.

Case Study 1: Xudong Wang, 2022

This study investigated the role of CEA family member 5 (CEACAM5) in lymph node (LN) metastasis of head and neck squamous cell carcinoma (HNSCC). Researchers compared CEACAM5 levels in HNSCC tissues with and without LN metastasis through transcriptome sequencing and analyzed associations with the N stage of LN metastasis using TCGA and GEO databases. CEACAM5's expression was also assessed across 33 common human tumors. CEACAM5 levels were higher in tumor tissues without LN metastasis and correlated with better prognosis in HNSCC patients. Functional studies in HNSCC cell lines revealed that CEACAM5 inhibits cell proliferation, migration, and promotes apoptosis. A mouse model confirmed CEACAM5's role in reducing LN metastasis.

Fig1. The protein expression of CEACAM5 in HNSCC tissues and adjacent normal tissues was analyzed by WB.

Fig2. Spearman's correlation between the expression of EMT-related transcription factors and that of CEACAM5 was analyzed based on data from TCGA.

Case Study 2: Du-San Baek, 2022

Neuro-endocrine prostate cancer (NEPC) is a highly aggressive form of prostate cancer that is responsible for 20% of deaths from metastatic castration-resistant prostate cancer (CRPC) and has a poor prognosis. Due to its unique cell-surface markers, standard treatments are ineffective. Researchers have discovered that CEACAM5 is a specific marker for NEPC and have developed a novel fully-human monoclonal antibody, 1G9, that targets this protein with high affinity and specificity. The antibody 1G9 does not bind off-target to other proteins. It has demonstrated CEACAM5-specific antibody-dependent cellular cytotoxicity (ADCC) against NEPC cells both in vitro and in vivo. Additionally, CAR-T cells engineered with 1G9 scFv have shown potent antitumor effects in a mouse model of prostate cancer.

Fig3. Binding of Fab 1G9 to different domains of CEACAM5 in an indirect ELISA.

Fig4. Cell surface expression level of CEACAM5 and cell surface binding of hIgG1 1G9 and 1C1.

CEACAM5 has several biochemical functions, for example, GPI anchor binding,identical protein binding,protein homodimerization activity. Some of the functions are cooperated with other proteins, some of the functions could acted by CEACAM5 itself. We selected most functions CEACAM5 had, and list some proteins which have the same functions with CEACAM5. You can find most of the proteins on our site.

CEACAM5 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 CEACAM5 here. Most of them are supplied by our site. Hope this information will be useful for your research of CEACAM5.

c3;llama single domain;draE;CEACAM1;CEACAM6;afaE3;UQCC2