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Testes-specific protease 50 promotes cell proliferation via inhibiting activin signaling

Oncogene volume 36, pages 5948–5957 (2017)Cite this article

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Abstract

Testes-specific protease 50 (TSP50), a novelly identified oncogene, has the capacity to induce cell proliferation, cell invasion and tumor growth. Further studies indicated that CAGA-luc (an activin-responsive reporter construct) reporter activity could be significantly suppressed by TSP50 overexpression, implying that the activin signaling may participate in TSP50-mediated cell proliferation. Here, we reported that TSP50 had an inhibitory effect on activin signaling. Mechanistic studies revealed that TSP50 could interact with ActRIIA, inhibit activin typeIreceptor (ActRIB) phosphorylation, repress Smad2/3 nuclear accumulation and finally promote cell proliferation by reducing the expression of activin signal target gene p27. Additionally, we found that ActRIB activation could reverse TSP50-mediated cell proliferation and tumor growth. Furthermore, analysis of human breast cancer specimens by immunohistochemistry indicated that TSP50 expression was negatively related to p-Smad2/3 and p27 protein levels. Most importantly, breast cancer diagnosis-related indicators such as tumor size, tumor grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) levels, were correlated well with TSP50/p-Samd2/3 and TSP50/p27 expression status. Thus, our studies revealed a novel regulatory mechanism underlying TSP50-induced cell proliferation and provided a new favorable intervention target for the treatment of breast cancer.

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Acknowledgements

This research was supported by grants from the National Natural Science Foundation of China (Grant no. 81272242 and 81502284), the Open Project of the National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University (No.130014561 and 130028683) and Jilin outstanding young talent Foundation (Grant no. 20170520031JH).

Author contributions

YLB and YXL conceived the experiments. ZBS, PW, LGS, CLY and YXH carried out experiments. ZBS, PW, JSN, TL, CF and YW analyzed the data. ZBS and PW wrote the manuscript.

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  1. Z-B Song and P Wu: These authors contributed equally to this work.

Authors and Affiliations

  1. National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, China

    Z-B Song, P Wu, C Fan, Y-L Bao, L-G Sun & C-L Yu

  2. Institute of Genetics and Cytology, Northeast Normal University, Changchun, China

    Z-B Song, Y Wu, L-G Sun, C-L Yu, Y-X Huang & Y-X Li

  3. Department of Pathology, the First Hospital of Jilin University, Changchun, China

    J-S Ni & T Liu

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  1. Z-B Song
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Correspondence to Y-L Bao or Y-X Li.

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Song, ZB., Wu, P., Ni, JS. et al. Testes-specific protease 50 promotes cell proliferation via inhibiting activin signaling. Oncogene 36, 5948–5957 (2017). https://doi.org/10.1038/onc.2017.198

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