title: TACC3 promotes stemness and is a potential therapeutic target in hepatocellular carcinoma.
abstract: Transforming acidic coiled-coil protein 3 (TACC3) is essential for cell mitosis and transcriptional functions. In the present study, we first demonstrated that both TACC3 protein and mRNA levels were elevated in HCC tissue samples compared with non-cancerous tissue biopsies according to western blot analyses, immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) assays. Moreover, high TACC3 expression was positively correlated with poor overall survival (OS) and disease-free survival (DFS) (p < 0.001). Using HCC cell lines, we then demonstrated that either TACC3 knockdown or treatment with the potential TACC3 inhibitor KHS101 suppressed cell growth and sphere formation as well as the expression of stem cell transcription factors, including Bmi1, c-Myc and Nanog. Silencing TACC3 may suppress the Wnt/β-catenin and PI3K/AKT signaling pathways, which regulate cancer stem cell-like characteristics. Taken together, these data suggest that TACC3 is enriched in HCC and that TACC3 down-regulation inhibits the proliferation, clonogenicity, and cancer stem cell-like phenotype of HCC cells. KHS101, a TACC3 inhibitor, may serve as a novel therapeutic agent for HCC patients with tumors characterized by high TACC3 expression.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.|Shandong Provincial Qianfoshan Hospital, Jinan, P. R. China.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Zhou
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.|Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Wang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Zhong-Guo
authors.initials: ZG
authors.lastname: Zhou
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Yao-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China.
authors.forename: Yue-Hua
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of General Internal Medicine, Ambulatory Treatment and Emergency Care, University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sai-Ching
authors.initials: SC
authors.lastname: Yeung
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Min-Shan
authors.initials: MS
authors.lastname: Chen
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Mu-Sheng
authors.initials: MS
authors.lastname: Zeng
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology; D014158:Transcription, Genetic; D014162:Transfection; D016896:Treatment Outcome
chemical_list: D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C120551:TACC3 protein, human
keywords: TACC3; hepatocellular carcinoma; stem cell