Miaomiao Dai
Chi Zhang
Kai Teng
Fengwei Wang
Hongbo Li
Weipeng Sun
Zihao Feng
Tiebang Kang
Xinyuan Guan
Ruihua Xu
Muyan Cai
Dan Xie
1 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China;
2 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250200, China;
3 Department of Musculoskeletal Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;
4 Department of Anorectal Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 510370, China;
5 Department of Urology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;
6 Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China;
7 Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
Funds: 201803040019), National Natural Science Foundation of China (81730072, 81672407 and 81872001, 81902411), Guangdong Natural Science Funds for Distinguished Young Scholar (No. 2015A030306001), National Postdoctoral Program for Innovative Talents (BX201700299) and China Postdoctoral Science Foundation (2018M643342).
We would like to thank all the members of the Xie laboratory for their valuable suggestions and comments. This work was supported by the grants of the National Key R&D Program of China (2017YFC1309001), Guangzhou Science and Technology Plan Projects (Health Medical Collaborative Innovation Program of Guangzhou
Received Date: 2020-02-22
Rev Recd Date:2020-06-28
Publish Date:2021-09-27
Abstract
Abstract
Hepatocellular carcinoma (HCC) 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 (KIF2C) 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 complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) 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.Keywords: KIF2C,
HCC,
TBC1D7,
mTORC1 signaling,
Wnt/β-catenin signaling
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