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CEACAM6 在人类癌症中的新兴作用(综述)。

The emerging roles of CEACAM6 in human cancer (Review).

机构信息

Department of Biliary‑Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P.R. China.

出版信息

Int J Oncol. 2024 Mar;64(3). doi: 10.3892/ijo.2024.5615. Epub 2024 Jan 19.

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.

摘要

癌胚抗原相关细胞黏附分子 6(CEACAM6)是一种糖基磷脂酰肌醇锚定的细胞表面糖蛋白 CEA 家族的细胞黏附蛋白。大量研究表明,CEACAM6 在胰腺腺癌、乳腺癌、非小细胞肺癌、胃癌、结肠癌等多种癌症中普遍上调,促进肿瘤的进展、侵袭和转移。CEACAM6 的转录表达受多种因素的调节,包括 CD151/TGF-β1/Smad3 轴、微小 RNA(miRNA,miR)-146、miR-26a、miR-29a/b/c、miR-128、miR-1256 和 DNA 甲基化。此外,CEACAM6 蛋白在 Asn256 位的 N-糖基化由α-1,6-甘露糖基转移酶 6-β-N-乙酰氨基葡萄糖基转移酶介导。在下游信号通路方面,CEACAM6 通过增加 cyclin D1 和 cyclin-dependent kinase 4 蛋白水平促进肿瘤增殖。CEACAM6 可以通过 EGFR 直接或间接激活 ERK1/2/MAPK 或 SRC/黏着斑激酶/PI3K/AKT 通路,从而刺激肿瘤增殖、侵袭、迁移、抵抗失巢凋亡和化疗以及血管生成。本文综述了 CEACAM6 在癌症中的表达模式、生物学功能及其与预后的关系。总之,CEACAM6 可能是一种有价值的诊断生物标志物和潜在的治疗靶点,用于治疗人类过度表达 CEACAM6 的癌症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ddf/10836497/11764ef4ea68/ijo-64-03-05615-g00.jpg

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