Autophagy mediated by arginine depletion activation of the nutrient sensor GCN2 contributes to interferon-gamma-induced malignant transformation of primary bovine mammary epithelial cells
文献类型： 外文期刊
第一作者： Xia, X-J
作者： Xia, X-J;Che, Y-Y;Lei, L-C;Gao, Y-Y;Zhao, S.;Zhang, J.;Wang, L.;Ao, C-J;Yang, H-J;Wang, J-Q
作者机构：
期刊名称：CELL DEATH DISCOVERY （ 影响因子：5.241； 五年影响因子：5.302 ）
ISSN：
年卷期： 2016 年 2 卷
页码：
收录情况： SCI
摘要： Autophagy has been linked to the regulation of both the prevention and progression of cancer. IFN-gamma has been shown to induce autophagy in multiple cell lines in vitro. However, whether IFN-gamma can induce autophagy and whether autophagy promotes malignant transformation in healthy lactating bovine mammary epithelial cells (BMECs) remain unclear. Here, we provide the first evidence of the correlation between IFN-gamma treatment, autophagy and malignant transformation and of the mechanism underlying IFN-gamma-induced autophagy and subsequent malignant transformation in primary BMECs. IFN-gamma levels were significantly increased in cattle that received normal long-term dietary corn straw (CS) roughage supplementation. In addition, an increase in autophagy was clearly observed in the BMECs from the mammary tissue of cows expressing high levels of IFN-gamma. In vitro, autophagy was clearly induced in primary BMECs by IFN-gamma within 24 h. This induced autophagy could subsequently promote dramatic primary BMEC transformation. Furthermore, we found that IFN-gamma promoted arginine depletion, activated the general control nonderepressible-2 kinase (GCN2) signalling pathway and resulted in an increase in autophagic flux and the amount of autophagy in BMECs. Overall, our findings are the first to demonstrate that arginine depletion and kinase GCN2 expression mediate IFN-gamma-induced autophagy that may promote malignant progression and that immunometabolism, autophagy and cancer are strongly correlated. These results suggest new directions and paths for preventing and treating breast cancer in relation to diet.
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