Department of Gynaecological Oncology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK.
School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, UK.
Carcinogenesis. 2021 Apr 17;42(3):327-343. doi: 10.1093/carcin/bgab010.
MUC16 (the cancer antigen CA125) is the most commonly used serum biomarker in epithelial ovarian cancer, with increasing levels reflecting disease progression. It is a transmembrane glycoprotein with multiple isoforms, undergoing significant changes through the metastatic process. Aberrant glycosylation and cleavage with overexpression of a small membrane-bound fragment consist MUC16-related mechanisms that enhance malignant potential. Even MUC16 knockdown can induce an aggressive phenotype but can also increase susceptibility to chemotherapy. Variable MUC16 functions help ovarian cancer cells avoid immune cytotoxicity, survive inside ascites and form metastases. This review provides a comprehensive insight into MUC16 transformations and interactions, with description of activated oncogenic signalling pathways, and adds new elements on the role of its differential glycosylation. By following the journey of the molecule from pre-malignant states to advanced stages of disease it demonstrates its behaviour, in relation to the phenotypic shifts and progression of ovarian cancer. Additionally, it presents proposed differences of MUC16 structure in normal/benign conditions and epithelial ovarian malignancy.
MUC16（肿瘤相关抗原 CA125）是上皮性卵巢癌最常用的血清生物标志物，其水平的升高反映了疾病的进展。它是一种跨膜糖蛋白，有多种亚型，在转移过程中会发生显著变化。异常糖基化和小膜结合片段的过度表达导致 MUC16 相关机制增强恶性潜能。即使 MUC16 敲低也能诱导侵袭表型，但也会增加对化疗的敏感性。MUC16 的功能多变有助于卵巢癌细胞逃避免疫细胞毒性，在腹水内存活并形成转移。本文全面深入地探讨了 MUC16 的转化和相互作用，描述了激活的致癌信号通路，并增加了其差异糖基化作用的新内容。通过追踪该分子从癌前状态到疾病晚期的过程，展示了其与卵巢癌表型转变和进展相关的行为。此外，还提出了在正常/良性状态和上皮性卵巢恶性肿瘤中 MUC16 结构的差异。
