Abstract
MUC16/CA125 has been identified as a prominent cancer biomarker, especially for epithelial ovarian cancers, in clinical test for over three decades. Due to its huge mass, limited knowledge of MUC16 was acquired previously. By utilizing a well characterized self-made MUC16 monoclonal antibody, we identified the endogenous interaction between a C-terminal fragment of MUC16 (MUC16C) and β-catenin for the first time, and further elucidated that trans-activation domain of β-catenin is required for this interaction. Such interaction could activate the Wnt/β-catenin signaling pathway by facilitating cytosol-nucleus transportation of β-catenin, consequently induce cell proliferation and the migration, eventually lead to tumorigenesis and metastasis in nude mice. Consistently, knockdown of MUC16 significantly weakened the capabilities of cells for proliferation and migration. Based on our discovery, we suggest that MUC16 appears as an attractive target for the development of effective anticancer drugs.
Highlights
Mucin 16 (MUC16) is the largest glycoprotein (3-5 million Da) in the Mucins family, which provides lubrication by forming mucous barriers to protect epithelial tissues from foreign insults [1,2,3]
The expression of MUC16 in various cell lines was checked with our self-made MUC16 antibody which can detect specific endogenous MUC16 around 250KD (A full gel picture of Western blot was shown in Supplementary Figure S1)
This MUC16 monoclonal antibody was obtain through the hybridoma technology with a C-terminal fragment, and it was well characterized by Western blot (Figure 1A), immunoprecipitation (Figure 1C), shRNA (Figure 5B), immunostaining (Supplementary Figure S2A) etc
Summary
Mucin 16 (MUC16) is the largest glycoprotein (3-5 million Da) in the Mucins family, which provides lubrication by forming mucous (chemical) barriers to protect epithelial tissues from foreign insults [1,2,3]. Compared with other mucin family members, the expression of MUC16 is very limited [9]. It is expressed by normal bronchial, endometrial, ovarian and corneal epithelial cells [10,11,12,13], and has evolved from the proteoglycan, agrin [14]. The extracellular region of over-expressed MUC16 in epithelial ovarian carcinoma can be cleaved from cell surface to become circulating elements in the blood, which is a well-established ovarian cancer marker for clinical diagnosis, known as CA125 [15,16,17,18,19,20]. Functions and molecular mechanisms of MUC16 are still largely unclear, owing to its relatively late identification and the difficulties in analyzing a protein of its enormous size [8, 9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
