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SMURF1, a promoter of tumor cell progression?

Cancer Gene Therapy volume 28, pages 551–565 (2021)Cite this article

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Abstract

Overexpression of HECT-type E3 ubiquitin ligase SMURF1 is correlated with poor prognosis in patients with various cancers, such as glioblastoma, colon cancer, and clear cell renal cell carcinoma. SMURF1 acts as a tumor promoter by ubiquitination modification and/or degradation of tumor-suppressing proteins. Combined treatment of Smurf1 knockdown with rapamycin showed collaborative antitumor effects in mice. This review described the role of HECT, WW, and C2 domains in regulating SMURF1 substrate selection. We summarized up to date SMURF1 substrates regulating different type cell signaling, thus, accelerating tumor progression, invasion, and metastasis. Furthermore, the downregulation of SMURF1 expression, inhibition of its E3 activity and regulation of its specificity to substrates prevent tumor progression. The potential application of SMURF1 regulators, specifically, wisely choose certain drugs by blocking SMURF1 selectivity in tumor suppressors, to develop novel anticancer treatments.

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Fig. 1: Regulators and substrates of SMURF1.
Fig. 2: SMURF1 related antitumor drugs.

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Acknowledgements

This work was supported by grants from Beijing Natural Science Foundation (Z190018), The Natural Science Foundation of China (81870123), China Postdoctoral Science Foundation Grant (2018M641206), and the National Science Foundation for Young Scientists of China (81902545).

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  1. These authors contributed equally: Qin Xia, Yang Li

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  1. School of Life Science, Beijing Institute of Technology, Beijing, China

    Qin Xia, Yang Li, Da Han & Lei Dong

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All authors reviewed and approved the final manuscript. Q.X. and Y.L. contributed to the conception and design of paper. Y.L. drafted the paper. Q.X. provided useful comments and suggestions. L.D. and Q.X. revised the paper.

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Xia, Q., Li, Y., Han, D. et al. SMURF1, a promoter of tumor cell progression?. Cancer Gene Ther 28, 551–565 (2021). https://doi.org/10.1038/s41417-020-00255-8

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