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HOXB9 promotes epithelial-to-mesenchymal transition via transforming growth factor-β1 pathway in hepatocellular carcinoma cells

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Abstract

The function of the epithelial-to-mesenchymal transition (EMT) during hepatocellular carcinoma (HCC) progression is well established. However, the regulatory mechanisms modulating this phenomenon remain unclear. Homeobox B9 (HOXB9) has been proposed as an oncogene in many cancer developments, but its function and underlying mechanisms in HCC metastasis remain unknown. HOXB9 modulates EMT through the transforming growth factor-β1 (TGF-β1) pathway, which is a recognized regulator of EMT in HCC cells. The knockdown of HOXB9 decreased the migration and invasion of HCC cells. Conversely, the HOXB9 overexpression led to an increase in the above-mentioned phenotypes in HCC cells. Further analysis of HOXB9-regulated cellular functions showed the ability of this transcription factor to induce EMT. Moreover, we demonstrated that the TGF-β1 pathway is important in HOXB9-induced EMT in HCC cells. These findings define a novel cellular mechanism regulated by HOXB9, which controls EMT phenotype in HCC. This study is the first to illustrate the pivotal function of HOXB9 in regulating the metastatic behavior of HCC cells.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (NSFC H1617).

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Authors and Affiliations

  1. Department of Radiology, Second Affiliated Hospital of Dalian Medical University, No. 467 Zhongshan Street, Dalian, 116027, China

    Lin Sha

  2. Department of Laparoscopic Surgery, First Affiliated Hospital of Dalian Medical University, No. 193 Lianhe Street, Shahekou District, Dalian, 116001, China

    Lei Dong

  3. Department of Pathology, Second Affiliated Hospital of Dalian Medical University, No. 467 Zhongshan Street, Dalian, 116027, China

    Li Lv

  4. Department of Emergency, Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian, 116001, China

    Lizhi Bai

  5. Department of Oncology, Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian, 116001, China

    Xuening Ji

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  1. Lin Sha
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  2. Lei Dong
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  3. Li Lv
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  4. Lizhi Bai
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  5. Xuening Ji
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Correspondence to Lei Dong or Xuening Ji.

Additional information

Lin Sha and Lei Dong have contributed equally to this work.

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Sha, L., Dong, L., Lv, L. et al. HOXB9 promotes epithelial-to-mesenchymal transition via transforming growth factor-β1 pathway in hepatocellular carcinoma cells. Clin Exp Med 15, 55–64 (2015). https://doi.org/10.1007/s10238-014-0276-7

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  • DOI: https://doi.org/10.1007/s10238-014-0276-7

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