The evolving role of MUC16 (CA125) in the transformation of ovarian cells and the progression of neoplasia

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.

Automated summary

MUC16, also known as CA125, is a commonly used biomarker in epithelial ovarian cancer, with increasing levels indicating disease progression. It is a glycoprotein with multiple isoforms that undergo significant changes during the metastatic process. Aberrant glycosylation and cleavage contribute to enhancing malignant potential through overexpression of a small membrane-bound fragment related to MUC16. Knockdown of MUC16 can induce aggressive phenotypes but also increase susceptibility to chemotherapy, with variable functions helping cancer cells evade immune cytotoxicity and form metastases. This review comprehensively explores the transformations and interactions of MUC16 in ovarian cancer, shedding light on its role in disease progression and potential differences in structure between normal and malignant conditions.