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Nck1 promotes the progression of ovarian carcinoma by enhancing the PI3K/AKT/p70S6K signaling

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Abstract

Non-catalytic region of tyrosine kinase adaptor protein 1 (Nck1) is crucial for the progression of cancers. However, little is known on the role of Nck1 in the progression of ovarian carcinoma (OC). Here, we show that Nck1 expression is up-regulated in 176 OC tissues, compared with non-carcinoma ovarian tissues, and the up-regulated Nck1 expression is associated with the aggressiveness of OC and shorter overall and disease-free survival in this population. Higher Nck1 expression was an independent risk factor for poor prognosis of OC. Furthermore, Nck1 silencing by short hairpin RNA (shRNA) technology significantly inhibited the proliferation, migration and invasion of OC cells in vitro and the growth and metastasis of implanted OC tumors in vivo. Human kinase phosphorylation array indicated that Nck1 silencing significantly reduced the relative levels of 11 kinase expression and phosphorylation in OC cells, particularly for decreased levels of p70S6 kinase (p70S6K) and protein kinase B (AKT) expression in SKOV3 cells. Actually, Nck1 silencing significantly decreased PI3K and AKT expression, and reduced AKT and p70S6K phosphorylation while Nck1 over-expression had opposite effects in OC cells. Therefore, our data indicate that Nck1 promotes the progression of OC by enhancing the PI3k/AKT/p70S6K signaling in OC. Our findings suggest that Nck1 expression may be valuable for evaluating the prognosis of OC and as a target for design of new therapies for OC.

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Acknowledgements

The authors thank the Laboratory Research Center, the First Affiliated Hospital of Chongqing Medical University for their experimental supplies.

Funding

This study was supported by a grant from the National Natural Science Foundation of China (Grant No. 81372800).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuzhong District, Chongqing, 400016, China

    **aohan Liu, **g Zhang, Zhaoning Duan & Liangdan Tang

  2. Department of Obstetrics and Gynecology, Union Affiliated Hospital of Fujian Medical University, Fuzhou, 300010, China

    **ushan Feng

  3. Chongqing Medical University, Chongqing, 400016, China

    Yang Yu & Min He

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Contributions

XL, JZ and LT designed the experiments. MH collected tissue samples. XL, JZ, ZD, XF and YY carried out the experiments. XL and XF analyzed the experimental results. XL and LT wrote the manuscript.

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Correspondence to Liangdan Tang.

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The authors declare that they have no competing interests.

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The human and animal experimental protocols were approved by the Ethical Review Board of the First Affiliated Hospital of Chongqing Medical University, Chongqing, China (No. 20181601). Written informed consent in accordance with the Declaration of Helsinki was obtained from all the enrolled patients for the use of their tissue specimens. All experiments on animals followed the Laboratory Animal Guideline.

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Liu, X., Zhang, J., Duan, Z. et al. Nck1 promotes the progression of ovarian carcinoma by enhancing the PI3K/AKT/p70S6K signaling. Human Cell 33, 768–779 (2020). https://doi.org/10.1007/s13577-020-00344-8

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