Calcyclin-binding protein contributes to cholangiocarcinoma progression by inhibiting ubiquitination of MCM2  

作　　者：YUSEN ZHANG LIPING LIU BIWEI LUO HONGGUI TANG XIAOFANG YU SHIYUN BAO 

机构地区：[1]Department of Hepatobiliary and Pancrease Surgery,The Second Clinical Medical College,Jinan University(Shenzhen People’s Hospital),Shenzhen,518020,China [2]Department of General Surgery,The Second Clinical Medical College,Jinan University(Shenzhen People’s Hospital),Shenzhen,518020,China [3]Department of Hepatobiliary and Pancrease Surgery,The First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,518020,China

出　　处：《Oncology Research》2023年第3期317-331,共15页肿瘤学研究（英文）

基　　金：funded by Shenzhen Key Medical Discipline Construction Fund(No.SZXK015);Guangdong Provincial Key Clinical Specialty Construction Project,National Key Clinical Specialty Construction Project and Guangdong Medical Science and Technology Research Fund(No.A2021230).

摘　　要：Background:Cholangiocarcinoma(CCA)represents the epithelial cell cancer with high aggressiveness whose five-year survival rate is poor with standard treatment.Calcyclin-binding protein(CACYBP)shows aberrant expression within several malignant tumors,but the role of CACYBP in CCA remains unknown.Methods:Immunohistochemical(IHC)analysis was used to identify CACYBP overexpression in clinical samples of CCA patients.Moreover,its correlation with clinical outcome was revealed.Furthermore,CACYBP’s effect on CCA cell growth and invasion was investigated in vitro and in vivo using loss-of-function experiments.Results:CACYBP showed up-regulation in CCA,which predicts the dismal prognostic outcome.CACYBP had an important effect on in-vitro and in-vivo cancer cell proliferation and migration.Additionally,knockdown of CACYBP weakened protein stability by promoting ubiquitination of MCM2.Accordingly,MCM2 up-regulation partly reversed CACYBP deficiency’s inhibition against cancer cell viability and invasion.Thus,MCM2 might drive CCA development by Wnt/β-catenin pathway.Conclusions:CACYBP exerted a tumor-promoting role in CCA by suppressing ubiquitination of MCM2 and activating Wnt/β-catenin pathway,hence revealing that it may be the possible therapeutic target for CCA treatment.

关 键 词：CACYBP CCA UBIQUITINATION Wnt/β-catenin pathway Prognosis 

分 类 号：R735.8[医药卫生—肿瘤]