Panoply™ Human MUC16 Knockdown Stable Cell Line

MUC16/CA125 has been clinically validated as an important tumor biomarker, particularly in epithelial ovarian cancer, for over three decades. Due to its large molecular weight, previous research on it has been limited. Here, researchers, utilizing a previously characterized, in-house monoclonal antibody against MUC16, identified for the first time an endogenous interaction between the C-terminal fragment of MUC16 (MUC16C) and β-catenin, further elucidating that this interaction requires the transactivation domain of β-catenin. This interaction activates the Wnt/β-catenin signaling pathway by promoting cytoplasmic-nuclear translocation of β-catenin, thereby inducing cell proliferation and migration, ultimately leading to tumor formation and metastasis in nude mice. Knockdown of the MUC16 gene significantly reduced cell proliferation and migration. Therefore, MUC16 represents an attractive target for the development of effective anticancer drugs.

Studies have shown that decreased MUC16 mRNA levels are associated with decreased mRNA levels of Wnt downstream genes (Cyclin D1, Axin2, c-Myc, Snail, and Survivin) and two EMT markers (Vimentin and Fibronectin), while increased mRNA levels of another EMT marker, E-cadherin (Figure 1A). Furthermore, in MUC16-knockdown SKBR-3 cells, protein levels of three Wnt downstream genes, Cyclin D1, c-Myc, and Axin2, were also decreased, as confirmed by two independent short-chain RNAs targeting MUC16 (Figure 1B). CCK8 assays demonstrated that MUC16 knockdown inhibited SKBR-3 cell proliferation (Figure 1C). This finding was supported by results from a colony formation assay: compared with control cells, MUC16-knockdown SKBR-3 cells exhibited reduced colony formation (Figure 1D). Furthermore, knockdown of MUC16 in SKBR-3 cells inhibited their migration and invasion abilities (Figure 1E). Therefore, MUC16 gene knockdown can reduce cell proliferation and migration ability.

Figure 1. MUC16 knockdown reduces proliferation and metastasis of SKBR-3 cells. (Liu Q, et al., 2016)