Alcohol is a well-known risk factor for hepatocellular carcinoma. Autophagy plays a dual role in liver cancer, as it suppresses tumor initiation and promotes tumor progression. Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy, which is impaired in alcohol-related liver disease. However, the role of TFEB in alcohol-associated liver carcinogenesis is unknown. Liver-specific Tfeb knockout (KO) mice and their matched wild-type (WT) littermates were injected with the carcinogen diethylnitrosamine (DEN), followed by chronic ethanol feeding. We found that the numbers of both total and larger tumors increased significantly in DEN-treated mice fed with ethanol diet than in mice fed with control diet. Although the number of tumors was not different between WT and L-Tfeb KO mice fed either control or ethanol diet, the number of larger tumors was less in L-Tfeb KO mice than in WT mice. To our surprise, no differences were found in liver injury, steatosis, inflammation, ductular reaction, fibrosis, and tumor cell proliferation in DEN-treated mice fed ethanol. However, the levels of glypican 3, a marker of malignant hepatocellular carcinoma, markedly decreased in DEN-treated L-Tfeb KO mice fed ethanol in comparison to the WT mice. Our findings indicate that chronic ethanol feeding promotes DEN-initiated liver tumor development, which tends to be attenuated by genetic deletion of hepatic TFEB.

Loss of Hepatic Transcription Factor EB Attenuates Alcohol-Associated Liver Carcinogenesis / Chao, Xiaojuan; Wang, Shaogui; Hlobik, Madeline; Ballabio, Andrea; Ni, Hong-Min; Ding, Wen-Xing. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - (2021). [10.1016/j.ajpath.2021.10.004]

Loss of Hepatic Transcription Factor EB Attenuates Alcohol-Associated Liver Carcinogenesis

Ballabio, Andrea;
2021

Abstract

Alcohol is a well-known risk factor for hepatocellular carcinoma. Autophagy plays a dual role in liver cancer, as it suppresses tumor initiation and promotes tumor progression. Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy, which is impaired in alcohol-related liver disease. However, the role of TFEB in alcohol-associated liver carcinogenesis is unknown. Liver-specific Tfeb knockout (KO) mice and their matched wild-type (WT) littermates were injected with the carcinogen diethylnitrosamine (DEN), followed by chronic ethanol feeding. We found that the numbers of both total and larger tumors increased significantly in DEN-treated mice fed with ethanol diet than in mice fed with control diet. Although the number of tumors was not different between WT and L-Tfeb KO mice fed either control or ethanol diet, the number of larger tumors was less in L-Tfeb KO mice than in WT mice. To our surprise, no differences were found in liver injury, steatosis, inflammation, ductular reaction, fibrosis, and tumor cell proliferation in DEN-treated mice fed ethanol. However, the levels of glypican 3, a marker of malignant hepatocellular carcinoma, markedly decreased in DEN-treated L-Tfeb KO mice fed ethanol in comparison to the WT mice. Our findings indicate that chronic ethanol feeding promotes DEN-initiated liver tumor development, which tends to be attenuated by genetic deletion of hepatic TFEB.
2021
Loss of Hepatic Transcription Factor EB Attenuates Alcohol-Associated Liver Carcinogenesis / Chao, Xiaojuan; Wang, Shaogui; Hlobik, Madeline; Ballabio, Andrea; Ni, Hong-Min; Ding, Wen-Xing. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - (2021). [10.1016/j.ajpath.2021.10.004]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/863042
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