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LRP16 prevents hepatocellular carcinoma progression through regulation of Wnt/β-catenin signaling

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Abstract

Elevated LRP16 expression is associated with poor clinical outcomes in multiple malignancies. We detected LRP16 expression in hepatocellular carcinoma (HCC) and found that it was downregulated in tumor samples and HCC cell lines. In a cohort of 80 HCC patients, high level of LRP16 expression in HCC tumors was associated with well differentiation, less lymph node metastasis, and good overall survival (OS). Overexpression of LRP16 in the HepG2 and MHCC-97L cell lines increased cell apoptosis, attenuated cell proliferation, migration, and invasion ability in vitro, and drastically diminished tumor growth and metastasis in vivo. Silencing LRP16 in HCC-LM3 and SMMC-7721 cell lines showed opposite results. Microarray evaluation of tumor cells overexpressing LRP16 revealed the effects on decreased activity in the Wnt signaling pathway. These results were confirmed by qRT-PCR and Western blots. Furthermore, inhibition of Wnt signaling decreased proliferation, migration, and invasion of HCC cell lines. Mechanism conducted showed that LRP16 overexpression could prevent β-catenin from entering the nucleus. Our study demonstrated that LRP16 suppresses tumor growth in HCC by modulating Wnt/β-catenin signaling.

Key messages

  • LRP16 was low expression in HCC tissue and cell lines.

  • Low expression of LRP16 in HCC was associated with poor prognosis.

  • LRP16 inhibits activation of the Wnt/β-catenin pathway in HCC.

  • LRP16 prevents β-catenin from entering the nucleus.

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Acknowledgements

We thank Zizheng Wang at the Hepatological Surgery Department of PLA for his analysis assistance.

Funding

This work was supported by grants from the Ministry of Science & Technology (“973” projects) (No. 2012CB917104) and the National Natural Science Foundation of China (No. 81341069; 81172853).

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Authors and Affiliations

  1. Department of Immunology, School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China

    Lijuan Shao

  2. PLA General Hospital Cancer Center, PLA Postgraduate School of Medicine, Beijing, 100001, People’s Republic of China

    Lijuan Shao, Lingxiong Wang, Fei Pan, Liangliang Wu, Lijun Zhang, Minggen Hu & Kexing Fan

  3. International Joint Cancer Institute, The Second Military Medical University, Shanghai, 200433, People’s Republic of China

    Lijuan Shao & Kexing Fan

  4. Department of General Surgery, Changhai Hospital, The Second Military Medical University, 800 Xiangyin Road, Shanghai, 200040, People’s Republic of China

    Wei Jing

  5. Department of Stomatology, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, People’s Republic of China

    Pan Yang

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  1. Lijuan Shao
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Shao, L., Jing, W., Wang, L. et al. LRP16 prevents hepatocellular carcinoma progression through regulation of Wnt/β-catenin signaling. J Mol Med 96, 547–558 (2018). https://doi.org/10.1007/s00109-018-1639-4

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  • DOI: https://doi.org/10.1007/s00109-018-1639-4

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