Oncotarget

Research Papers:

C-terminus of MUC16 activates Wnt signaling pathway through its interaction with β-catenin to promote tumorigenesis and metastasis

Qi Liu, Zhen Cheng, Lianzhong Luo, Yun Yang, Zhenzhu Zhang, Huanhuan Ma, Tao Chen, Xi Huang, Shu-Yong Lin, Meijun Jin, Qinxi Li and Xiaotong Li _

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Oncotarget. 2016; 7:36800-36813. https://doi.org/10.18632/oncotarget.9191

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Abstract

Qi Liu1, Zhen Cheng1, Lianzhong Luo2, Yun Yang3, Zhenzhu Zhang1, Huanhuan Ma1, Tao Chen1, Xi Huang1, Shu-Yong Lin1, Meijun Jin1, Qinxi Li1, Xiaotong Li1

1State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Fujian 361102, China

2Central Laboratory, Xiamen Medical College, Xiamen, Fujian 361008, China

3School of Basic Medical Sciences, Xinxiang Medical University, Henan 453003, China

Correspondence to:

Xiaotong Li, e-mail: [email protected]

Qinxi Li, e-mail: [email protected]

Keywords: MUC16, C-terminus, β-catenin, Wnt signaling, tumorigenesis

Received: December 09, 2015    Accepted: April 18, 2016    Published: May 5, 2016

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.


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