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.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer and the third most common cause of cancer-related mortality in the world; HCC is a serious global health problem [1]
This study explored increased Transforming acidic coiled-coil protein 3 (TACC3) expression in HCC and the dynamic interplay between stem cell-like characteristics and signaling pathways to assess whether TACC3 is a novel target for HCC therapy
We determined that TACC3 might be an oncogene that plays an important role in tumorigenesis, differentiation, amplification and metastasis in HCC
Summary
Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer and the third most common cause of cancer-related mortality in the world; HCC is a serious global health problem [1]. An oral multikinase inhibitor of the VEGF www.impactjournals.com/oncotarget and PDGF receptors, has been confirmed in clinical trials to be effective and safe in patients with advanced HCC [2, 8, 10, 11]. All of these clinical trials were adjusted for advanced-stage tumors, the results were still not promising. Inhibiting CSC functions will reduce tumor proliferation and likely cure malignant tumors Signaling pathways such as the Wnt, Notch, Shh and PI3K/AKT/mTOR pathways play important roles in the regulation of HCC stem cells [13,14,15,16]. Identifying factors that block one or more of these signaling pathways might lead to the inhibition of cancer stem-like capabilities
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