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

• DOI: 10.3389/fphar.2021.659325
• Publication Date: 2021-06-08T08:05:34Z
• Authors: Danping Huang; Bowen Yang; Yaoyao Yao; Mianmian Liao; Yu Zhang; Yihao Zeng; Fengxue Zhang; Neng Wang; Guangdong Tong
• Keywords: Metastasis suppressor

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 proliferation, migration invasion HBV-associated HCC cells. The following network biological analyses predicted that mainly targeted Caveolin-1 (Cav-1) induce effects, Wnt/β-catenin pathway one core against HCC. Further experimental validation implied Cav-1 overexpression promoted metastasis by stabilizing β-catenin, while administration induced autophagic degradation Cav-1, activated Akt/GSK3β-mediated proteasome β-catenin via ubiquitination activation, subsequently attenuated metastasis-promoting effect Cav-1. addition, anti-cancer further confirmed vivo ex experiments. It inhibited tumor growth both mice liver xenograft zebrafish xenotransplantation models. Taken together, our study only highlights novel function suppressing HCC, but it also addresses critical role mediating Akt/GSK3β/β-catenin axis control late-phase progression.