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作者

Shi Wei Miaomiao Dai Chi Zhang Kai Teng Fengwei Wang Hongbo Li Weipeng Sun Zihao Feng Tiebang Kang Xinyuan Guan Ruihua Xu Muyan Cai Dan Xie

作者单位

State Key Laboratory of Oncology in South China，Collaborative Innovation Center for Cancer Medicine，Sun Yat-sen University Cancer Center，Guangzhou 510060，China；Department of Radiation Oncology，Shandong Cancer Hospital and Institute，Shandong First Medical University and Shandong Academy of Medical Sciences，Jinan 250200，China；Department of Musculoskeletal Oncology，the First Affiliated Hospital，Sun Yat-sen University，Guangzhou 510080，China；Department of Anorectal Surgery，the First Affiliated Hospital of Zhengzhou University，Zhengzhou 510370，China；Department of Urology，the First Affiliated Hospital，Sun Yat-sen University，Guangzhou 510080，China；Department of Clinical Oncology，Li Ka Shing Faculty of Medicine，The University of Hong Kong，Pokfulam，Hong Kong SAR，China；State Key Laboratory of Oncology in South China，Collaborative Innovation Center for Cancer Medicine，Sun Yat-sen University Cancer Center，Guangzhou 510060，China；Department of Pathology，Sun Yat-sen University Cancer Center，Guangzhou 510060，China

刊名

蛋白质与细胞

年份

2021

卷号

第12卷

期号

第10期

页码

788-809

ISSN

1674-800X

关键词

KIF2C HCC TBC1D7 mTORC1 signaling Wnt/β-catenin signaling

摘要

Hepatocellular carcinoma is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide.HCC is refractory to many standard cancer treatments and the prognosis is often poor,highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments.Kinesin family member 2C is reported to be highly expressed in several human tumors.Nevertheless,the molecular mechanisms underlying the role of KIF2C in tumor dev...更多

Hepatocellular carcinoma is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide.HCC is refractory to many standard cancer treatments and the prognosis is often poor,highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments.Kinesin family member 2C is reported to be highly expressed in several human tumors.Nevertheless,the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated.In this study,we found that KIF2C expression was significantly upregulated in HCC,and that KIF2C up-regulation was associated with a poor prognosis.Utilizing both gain and loss of function assays,we showed that KIF2C promoted HCC cell proliferation,migration,invasion,and metastasis both in vitro and in vivo.Mechanistically,we identified TBC1D7 as a binding partner of KIF2C,and this interaction disrupts the formation of the TSC com-plex,resulting in the enhancement of mammalian target of rapamycin complex1 signal transduction.Additionally,we found that KIF2C is a direct target of the Wnt/β-catenin pathway,and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORC1 signaling.Thus,the results of our study establish a link between Wnt/β-catenin and mTORC1 signaling,which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC收起

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期刊