ER-residential Nogo-B accelerates NAFLD-associated HCC mediated by metabolic reprogramming of oxLDL lipophagy
Publication in refereed journal

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摘要Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome that elevates the risk of hepatocellular carcinoma (HCC). Although alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells, the deregulated metabolic modulation of HCC cells in the NAFLD progression remains obscure. Here, we discovers an endoplasmic reticulum-residential protein, Nogo-B, as a highly expressed metabolic modulator in both murine and human NAFLD-associated HCCs, which accelerates high-fat, high-carbohydrate diet-induced metabolic dysfunction and tumorigenicity. Mechanistically, CD36-mediated oxLDL uptake triggers CEBPβ expression to directly upregulate Nogo-B, which interacts with ATG5 to promote lipophagy leading to lysophosphatidic acid-enhanced YAP oncogenic activity. This CD36-Nogo-B-YAP pathway consequently reprograms oxLDL metabolism and induces carcinogenetic signaling for NAFLD-associated HCCs. Targeting the Nogo-B pathway may represent a therapeutic strategy for HCC arising from the metabolic syndrome.
著者Yuan TIAN, Bin YANG, Weinan QIU, Yajing HAO, Zhenxing ZHANG, Bo YANG, Nan LI, Shuqun CHENG, Zhangjun LIN, Yao-cheng RUI, Otto K. W. CHEUNG, Weiqin YANG, William K. K. WU, Yue-Sun CHEUNG, Paul B. S. LAI, Jianjun LUO, Joseph J. Y. SUNG, Runsheng CHEN, Hong-Yang WANG, Alfred S. L. CHENG, Pengyuan YANG
期刊名稱Nature Communications
出版年份2019
月份7
日期29
卷號10
出版社NATURE PUBLISHING GROUP
文章號碼3391
國際標準期刊號2041-1723
語言英式英語
Web of Science 學科類別Multidisciplinary Sciences;Science & Technology - Other Topics

上次更新時間 2020-20-09 於 00:45