Hepatic prohibitin 1 and methionine adenosyltransferase α1 defend against primary and secondary liver cancer metastasis

Wei Fan,DuoYao Cao,Bing Yang,Jiaohong Wang,Xiaomo Li, Diana Kitka,Tony W.H. Li,Sungyong You,Stephen Shiao,Alexandra Gangi,Edwin Posadas,Dolores Di Vizio,Maria Lauda Tomasi,Ekihiro Seki,José M. Mato,Heping Yang,Shelly C. Lu

Journal of Hepatology（2023）

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摘要

•Hepatic MMP-7 is induced when either PHB1 or MAT1A is downregulated.•PHB1-MAT1A represses while MAFG-FOSB activates MMP7 transcription via an AP-1 site.•MMP-7 is secreted in EVs and taken up by cancer cells to increase oncogenic activity.•Silencing MMP-7 blocked increased colorectal liver metastasis in Mat1a KO and Phb1+/- mice.•The presence of colorectal liver metastasis lowered MAT1A but raised MMP-7 expression in hepatocytes.

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关键词

Prohibitin 1,methionine adenosyltransferase 1A,matrix metalloproteinase-7,MAFG,FOSB,hepatocellular carcinoma,cholangiocarcinoma,colorectal cancer,metastasis

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