Carboxyl-terminal polypeptide fragment of MUC16 combing stathmin1 promotes gallbladder cancer cell migration and invasio
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ORIGINAL PAPER
Carboxyl-terminal polypeptide fragment of MUC16 combing stathmin1 promotes gallbladder cancer cell migration and invasion Kun Fan1,2,3,4 · Dexiang Zhang1 · Min Li2,3,4 · Sheng Shen2,3,4 · Jiwen Wang2,3,4 · Xiaojian Ni2,3,4 · Zijun Gong2,3,4 · Bohao Zheng2,3,4 · Zhihui Gao2,3,4 · Xiaoling Ni2,3,4 · Tao Suo2,3,4 · Han Liu2,3,4 · Houbao Liu1,2,3,4 Received: 18 July 2020 / Accepted: 30 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract CA-125, coded by MUC16 gene, is responsible to many kinds of tumor metastasis. However, the related mechanism remains unclear. We have established a novel manner to reveal gallbladder cancer metastasis related to serum CA-125 levels through the C-terminal polypeptide of MUC16 gene production. MUC16 C-terminal polypeptide significantly promoted gallbladder cancer cell migration and invasion in vitro. Mass spectrum indicated that interaction of MUC16 C-terminal fragment with the C-terminal domain of stathmin1 inhibited the phosphorylation of stathmin1 to promote the combination with tubulin. Stathmin1 knockdown inhibited the migration and invasion of gallbladder cancer cells in vitro and lung metastasis in vivo induced by MUC16 C-terminal polypeptide. The high expression level of MUC16c consistent with stathmin1 was also confirmed in gallbladder cancer tissues. Our study revealed the underlying mechanism of gallbladder cancer metastasis related to CA-125 levels, which was beneficial for CA-125 in gallbladder cancer diagnose and therapy. Keywords Gallbladder cancer · Stathmin1 · Microtubule · MUC16 C-terminal · Metastasis
Introduction Gallbladder cancer is a highly malignant tumor, accounting for the 80–85% of biliary tumor [1]. Many patients were diagnosed at advanced stages with metastasis [1], which could not been treated by surgical operation. The overall Kun Fan, Dexiang Zhang, and Min Li have been contributed equally to this article. * Tao Suo suo.tao@zs‑hospital.sh.cn * Han Liu liu.han@zs‑hospital.sh.cn * Houbao Liu liu.houbao@zs‑hospital.sh.cn 1
General Surgery Department, Zhongshan-Xuhui Hospital Affiliated to Fudan University, Shanghai, China
2
Department of General Surgery, Zhongshan Hospital, Fudan University, 180, Fenglin Road, Xuhui, Shanghai, China
3
Biliary Tract Disease Center of Zhongshan Hospital, Fudan University, Shanghai, China
4
Biliary Tract Disease Institute, Fudan University, Shanghai, China
survival of gallbladder cancer is mere 6 months, and 5-year survival rate is only 5% [2, 3]. Therefore, it is urgent to explore the metastatic mechanism for gallbladder cancer therapy. CA-125, coded by MUC16 gene, is an important tumor biomarker in diagnose and therapy. CA-125 is the only clinically reliable diagnostic marker for ovarian tumors indicating the progression and metastasis of ovarian tumors [4]. Moreover, high serological CA-125 levels also indicated pancreatic cancer metastasis and poor prognosis [5, 6]. It has reported that CA-125 could promote tumor cell proliferation and inhibit anti-
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