title: C-terminus of MUC16 activates Wnt signaling pathway through its interaction with β-catenin to promote tumorigenesis and metastasis.
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.
authors.affiliation: State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian 361102, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian 361102, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Central Laboratory, Xiamen Medical College, Xiamen, Fujian 361008, China.
authors.forename: Lianzhong
authors.initials: L
authors.lastname: Luo
authors.affiliation: School of Basic Medical Sciences, Xinxiang Medical University, Henan 453003, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian 361102, China.
authors.forename: Zhenzhu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian 361102, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Ma
authors.affiliation: State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian 361102, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian 361102, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian 361102, China.
authors.forename: Shu-Yong
authors.initials: SY
authors.lastname: Lin
authors.affiliation: State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian 361102, China.
authors.forename: Meijun
authors.initials: M
authors.lastname: Jin
authors.affiliation: State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian 361102, China.
authors.forename: Qinxi
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian 361102, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D018394:CA-125 Antigen / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D064593:Heterografts; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010446:Peptide Fragments; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D018394:CA-125 Antigen; C495270:CTNNB1 protein, human; C451759:MUC16 protein, human; D008565:Membrane Proteins; D010446:Peptide Fragments; D051176:beta Catenin
keywords: C-terminus; MUC16; Wnt signaling; tumorigenesis; β-catenin