Abstract
Aberrant Src kinase activity is known to be involved in a variety of human malignancies, whereas the regulatory mechanism of Src has not been completely clarified. Here, we demonstrated that tripartite motif containing 7 (TRIM7) directly interacted with Src, induced Lys48-linked polyubiquitination of Src and reduced the abundance of Src protein in hepatocellular carcinoma (HCC) cells. We further identified TRIM7 as a tumor suppressor in HCC cells through its negative modulation of the Src-mTORC1-S6K1 axis in vivo and in vitro in several HCC models. Moreover, we verified the dysregulated expression of TRIM7 in clinical liver cancer tissues and its negative correlation with Src protein in clinical HCC specimens. Overall, we demonstrated that TRIM7 suppressed HCC progression through its direct negative regulation of Src and modulation of the Src-mTORC1-S6K1 axis; thus, we provided a novel insight into the development of HCC and defined a promising therapeutic strategy for cancers with overactive Src by modulating TRIM7.
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All relevant data that support the findings of this study are available from the corresponding author upon request. Supplementary information is available at Cell Death & Differentiation’s website.
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Acknowledgements
This study was supported by the National Natural Science Foundation of China (no. 81672391, no.81972275, no.81472269, no.81602550, and no.81772626) and the Major Innovation Project of Shandong Province (no. 2018CXGC1217).
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Supplementary materials-The E3 ubiquitin ligase TRIM7 suppressed hepatocellular carcinoma progression by directly targeting Src protein
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Zhu, L., Qin, C., Li, T. et al. The E3 ubiquitin ligase TRIM7 suppressed hepatocellular carcinoma progression by directly targeting Src protein. Cell Death Differ 27, 1819–1831 (2020). https://doi.org/10.1038/s41418-019-0464-9
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DOI: https://doi.org/10.1038/s41418-019-0464-9
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