EAG1 enhances hepatocellular carcinoma proliferation by modulating SKP2 and metastasis through pseudopod formation


Ether-à-go-go-1 (EAG1), one of the potassium channels, is involved in various physiological processes and plays an important role in the tumorigenesis of many kinds of cancer. EAG1 is highly expressed in hepatocarcinoma cells and is closely related to clinical prognosis, but the molecular mechanism remains elusive. In this study, we verified that EAG1 promotes the proliferation of hepatocellular carcinoma (HCC) both in vitro and in vivo. It promotes cell cycle progression by inhibiting the ubiquitination of SKP2. In addition, EAG1 promotes the migration and invasion of HCC by promoting cell pseudopod formation. Furthermore, in a high-pressure plasmid-injected mouse liver orthotopic carcinoma model, astemizole, an EAG family blocker, can significantly inhibit the formation of liver cancer. Meanwhile, liver-specific EAG1 knockout mice show resistance to hepatocarcinogenesis. This research demonstrated that EAG1 plays an important role in the progression of HCC, and could be a potential therapeutic target for HCC.

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Fig. 1: EAG1 promoted cell proliferation of two HCC cell lines.
Fig. 2: Changes in EAG1 affected cell cycle progression and cell cycle-related proteins.
Fig. 3: EAG1 affected SKP2 protein degradation.
Fig. 4: EAG1 promoted cell proliferation by regulating SKP2.
Fig. 5: EAG1 promoted cell migration and invasion of HCC in vitro and in vivo.
Fig. 6: Inhibition of EAG1 prevented the HCC formation.
Fig. 7: Expression of EAG1 was upregulated in HCC tissues and positively correlated with SKP2.


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This work was supported by the National Natural Science Foundation of China (81272675 and 81870434) to PS, the Key Research and Development Plan of Zhejiang Province (2020C04003) to PS, the National S&T Major Project (2017ZX10203205) to SZ.

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Correspondence to Shusen Zheng or Penghong Song.

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Chen, J., Xuan, Z., Song, W. et al. EAG1 enhances hepatocellular carcinoma proliferation by modulating SKP2 and metastasis through pseudopod formation. Oncogene (2020). https://doi.org/10.1038/s41388-020-01522-6

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