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 oft...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 complexl(mTORCI)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 mTORCI signaling.Thus,the results of our study establish a link between Wnt/β-catenin and mTORCI signaling,which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.展开更多
基金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,201803040019)+3 种基金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)China Postdoctoral Science Foundation(2018M643342).
文摘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 complexl(mTORCI)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 mTORCI signaling.Thus,the results of our study establish a link between Wnt/β-catenin and mTORCI signaling,which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.
