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BMP10 suppresses hepatocellular carcinoma progression via PTPRS–STAT3 axis

Oncogene volume 38, pages 7281–7293 (2019)Cite this article

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Abstract

Bone morphogenetic protein 10 (BMP10), one member of the BMP family, is involved in various development events. Dysregulation of BMP10 has been observed in several diseases, including hypertensive cardiac hypertrophy, Hirschsprung disease and blood vessel formation. However, its role in liver cancer remains largely unknown. In this study, we reported that BMP10 was significantly downregulated in HCC at both mRNA and protein level. Decreased BMP10 was associated with bigger tumor size, worse TNM stage, earlier recurrence and poorer survival. BMP10 negatively regulated HCC cell proliferation in vitro and in vivo. Mechanism study revealed that BMP10 suppressed tumor cell growth by inhibiting STAT3 signaling. Interestingly, we found that cytoplasmic BMP10 interacted with both receptor protein tyrosine phosphatase sigma (PTPRS) and STAT3, which facilitated dephosphorylation of STAT3 by PTPRS. Altogether, our study has revealed the clinical significance of BMP10 in HCC, and suppression of HCC cell growth by BMP10 via PTPRS–STAT3 axis, providing a potential therapeutic strategy for targeting STAT3 signaling in HCC.

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Acknowledgements

We thank the New World Group for their Charitable Foundation to establish the Institute for Nutritional Sciences, SIBS, CAS-New World Joint laboratory, which have given full support to this study.

Funding

This work was supported by the National Key R&D Program of China (2018YFC1603002, 2018YFC1604404), the “Personalized Medicines—Molecular Signature-based Drug Discovery and Development”, Strategic Priority Research Program of the Chinese Academy of Sciences (Grant no. XDA12010316), and National Natural Science Foundation of China (31520103907, 81730083) to Dong Xie; and National Natural Science Foundation of China (31771538), Youth Innovation Promotion Association of Chinese Academy of Sciences fund and Sanofi-SIBS 2018 Young Faculty Award to Jing-Jing Li.

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Authors and Affiliations

  1. CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 200031, Shanghai, China

    Yan-Mei Yuan, Ning Ma, Er-Bin Zhang, Tian-Wei Chen, Hao Jiang, Fen-Fen Yin, Jing-Jing Wang, Feng-Kun Zhang, Qian-Zhi Ni, Jing-Jing Li & Dong Xie

  2. Key Laboratory of Translational Medicine, First People’s Hospital Affiliated, Huzhou University, 313000, Huzhou, China

    Xiang Wang

  3. Department of Surgery, First People’s Hospital Affiliated, Huzhou University, 313000, Huzhou, China

    Ying Bao

  4. Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 200438, Shanghai, China

    Kang Wang & Shu-Qun Cheng

  5. Department of General Surgery, Fengxian Hospital Affiliated to Southern Medical University, 6600 Nanfeng Road, 201499, Shanghai, China

    Xue-Li Zhang

  6. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, 27710, USA

    Xiao-Fan Wang

  7. School of Life Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, 201210, Shanghai, China

    Dong Xie

  8. NHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment, 100022, Beijing, China

    Dong Xie

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  1. Yan-Mei Yuan
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Correspondence to Jing-Jing Li or Dong Xie.

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Yuan, YM., Ma, N., Zhang, EB. et al. BMP10 suppresses hepatocellular carcinoma progression via PTPRS–STAT3 axis. Oncogene 38, 7281–7293 (2019). https://doi.org/10.1038/s41388-019-0943-y

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  • DOI: https://doi.org/10.1038/s41388-019-0943-y

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