The emerging roles of CEACAM6 in human cancer (Review)

Abstract

Carcinoembryonic antigen (CEA)‑related cell adhesion molecule 6 (CEACAM6) is a cell adhesion protein of the CEA family of glycosyl phosphatidyl inositol anchored cell surface glycoproteins. A wealth of research has demonstrated that CEACAM6 is generally upregulated in pancreatic adenocarcinoma, breast cancer, non‑small cell lung cancer, gastric cancer, colon cancer and other cancers and promotes tumor progression, invasion and metastasis. The transcriptional expression of CEACAM6 is regulated by various factors, including the CD151/TGF‑β1/Smad3 axis, microRNA (miR)‑146, miR‑26a, miR‑29a/b/c, miR‑128, miR‑1256 and DNA methylation. In addition, the N‑glycosylation of CEACAM6 protein at Asn256 is mediated by α‑1,6‑mannosylglycoptotein 6‑β‑N‑acetylglucosaminyltransferase. In terms of downstream signaling pathways, CEACAM6 promotes tumor proliferation by increasing levels of cyclin D1 and cyclin‑dependent kinase 4 proteins. CEACAM6 can activate the ERK1/2/MAPK or SRC/focal adhesion kinase/PI3K/AKT pathways directly or through EGFR, leading to stimulation of tumor proliferation, invasion, migration, resistance to anoikis and chemotherapy, as well as angiogenesis. This article provides a review of the expression pattern, biological function and relationship with prognosis of CEACAM6 in cancer. In summary, CEACAM6 may be a valuable diagnostic biomarker and potential therapeutic target for human cancers exhibiting overexpression of CEACAM6.

Keywords: CEACAM6; biomarker; cancer.

Figure 1

The CEACAM6 signaling pathways. In the upstream of the CEACAM6 signaling pathways, CD151 promotes SMAD3 phosphorylation via TGF-β1. This leads to the phosphorylation of SMAD3, which in turn promotes the transcription of CEACAM6. On the other hand, miR-146, miR-26a, miR-29a/b/c, miR-128 and miR-1256 inhibit the transcription of CEACAM6. The transcriptional expression of CEACAM6 is also regulated by promoter DNA methylation. In addition, MGAT5 facilitates N-glycosylation at Asn256 of the CEACAM6 protein. Downstream of the CEACAM6 signaling pathways, CEACAM6 promotes tumor proliferation by increasing cyclin D1 and CDK4 protein levels. CEACAM6 activates the ERK1/2/MAPK or SRC/FAK/PI3K/AKT pathways either directly or via EGFR to stimulate tumor proliferation, invasion, migration, resistance to anoikis and chemotherapy, as well as angiogenesis. FAK, focal adhesion kinase; MGAT5, α-1,6-mannosylglycoptotein 6-β-N-acetylglucosaminyltransferase; CDK, cyclin-dependent kinase; CEACAM6, carcinoembryonic antigen-related cell adhesion molecule 6.