Oncotarget

Research Papers:

TACC3 promotes stemness and is a potential therapeutic target in hepatocellular carcinoma

Dong-Sheng Zhou, Hong-Bo Wang, Zhong-Guo Zhou, Yao-Jun Zhang, Qian Zhong, Li Xu, Yue-Hua Huang, Sai-Ching Yeung, Min-Shan Chen and Mu-Sheng Zeng _

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Oncotarget. 2015; 6:24163-24177. https://doi.org/10.18632/oncotarget.4643

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Abstract

Dong-Sheng Zhou1,2,*, Hong-Bo Wang1,3,*, Zhong-Guo Zhou1,*, Yao-Jun Zhang1, Qian Zhong1, Li Xu1, Yue-Hua Huang3, Sai-Ching Yeung4,5, Min-Shan Chen1 and Mu-Sheng Zeng1

1 Sun Yat-sen University Cancer Center, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China

2 Shandong Provincial Qianfoshan Hospital, Jinan, P. R. China

3 Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P. R. China

4 Department of General Internal Medicine, Ambulatory Treatment and Emergency Care, University of Texas MD Anderson Cancer Center, Houston, TX, USA

5 Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, TX, USA

* These authors have contributed equally to this work

Correspondence to:

Min-Shan Chen, email:

Mu-Sheng Zeng, email:

Keywords: hepatocellular carcinoma, TACC3, stem cell

Received: April 21, 2015 Accepted: June 17, 2015 Published: June 25, 2015

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.


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