Autophagic Inhibition of Caveolin-1 by Compound Phyllanthus urinaria L. Activates Ubiquitination and Proteasome Degradation of β-catenin to Suppress Metastasis of Hepatitis B-Associated Hepatocellular Carcinoma.
Autophagic Inhibition of Caveolin-1 by Compound Phyllanthus urinaria L. Activates Ubiquitination and Proteasome Degradation of β-catenin to Suppress Metastasis of Hepatitis B-Associated Hepatocellular Carcinoma.
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复合叶下珠对 Caveolin-1 的自噬抑制。激活 β-catenin 的泛素化和蛋白酶体降解，抑制乙型肝炎相关肝细胞癌的转移。
DOI：
10.3389/fphar.2021.659325
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发表时间：
2021
影响因子：
5.6
通讯作者：
Tong G
中科院分区：
文献类型：
--
作者：
Huang D;Yang B;Yao Y;Liao M;Zhang Y;Zeng Y;Zhang F;Wang N;Tong G
Compound Phyllanthus urinaria L. (CP) is a traditional Chinese medicine (TCM) formula for cancer treatment in the clinic, particularly during progression of hepatitis B-associated hepatocellular carcinoma (HBV-associated HCC). Nevertheless, its anti-metastatic action and mechanisms are not well elucidated. In this study, CP was found to exert remarkable inhibitory effects on the proliferation, migration and invasion of HBV-associated HCC cells. The following network and biological analyses predicted that CP mainly targeted Caveolin-1 (Cav-1) to induce anti-metastatic effects, and Wnt/β-catenin pathway was one of the core mechanisms of CP action against HBV-associated HCC. Further experimental validation implied that Cav-1 overexpression promoted metastasis of HBV-associated HCC by stabilizing β-catenin, while CP administration induced autophagic degradation of Cav-1, activated the Akt/GSK3β-mediated proteasome degradation of β-catenin via ubiquitination activation, and subsequently attenuated the metastasis-promoting effect of Cav-1. In addition, the anti-cancer and anti-metastatic action of CP was further confirmed by in vivo and ex vivo experiments. It was found that CP inhibited the tumor growth and metastasis of HBV-associated HCC in both mice liver cancer xenograft and zebrafish xenotransplantation models. Taken together, our study not only highlights the novel function of CP formula in suppressing metastasis of HBV-associated HCC, but it also addresses the critical role of Cav-1 in mediating Akt/GSK3β/β-catenin axis to control the late-phase of cancer progression.
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影响因子：
29.4
作者：
El-Serag HB
通讯作者：
El-Serag HB
DOI：
10.1186/bcr3573
发表时间：
2013-11-07
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Drabsch Y;He S;Zhang L;Snaar-Jagalska BE;ten Dijke P
通讯作者：
ten Dijke P
影响因子：
45.3
作者：
Goessling, Wolfram;North, Trista E.;Zon, Leonard I.
通讯作者：
Zon, Leonard I.
DOI：
10.6004/jnccn.2017.7024
发表时间：
2018-01-01
影响因子：
13.4
作者：
Harding, James J.;Abu-Zeinah, Ghaith;Abou-Alfa, Ghassan K.
通讯作者：
Abou-Alfa, Ghassan K.
影响因子：
4.1
作者：
Cole, A;Frame, S;Cohen, P
通讯作者：
Cohen, P