Up-regulated acylglycerol kinase (AGK) expression associates with gastric cancer progression through the formation of a novel YAP1-AGK-positive loop.
Up-regulated acylglycerol kinase (AGK) expression associates with gastric cancer progression through the formation of a novel YAP1-AGK-positive loop.
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酰基甘油激酶（AGK）表达上调通过形成新型 YAP1-AGK 阳性环与胃癌进展相关
DOI：
10.1111/jcmm.15613
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发表时间：
2020-10
影响因子：
5.3
通讯作者：
Xiong J
中科院分区：
文献类型：
--
作者：
Huang S;Cao Y;Guo H;Yao Y;Li L;Chen J;Li J;Xiang X;Deng J;Xiong J
酰基甘油激酶（AGK）使用三磷酸腺苷（ATP）和酰基甘油在细胞中产生二磷酸腺苷（ADP）和酰基-sn-甘油3-磷酸。最近的证据表明，AGK表达失调与各种人类癌症的发展有关。本研究探讨AGK对胃癌细胞增殖和癌变的影响，并探讨其分子机制。AGK表达在胃癌中上调，并且与胃癌患者的不良预后相关。AGK过表达增加体外胃癌增殖、侵袭能力和上皮间质转化标志物的表达。相反，AGK表达的敲低降低了体外和裸鼠肿瘤细胞异种移植物中胃癌细胞的增殖。AGK与YAP 1在胃癌细胞和组织中的表达密切相关。YAP 1表达也通过TEAD与AGK基因启动子的结合转录诱导AGK表达。然而，AGK的表达抑制了Hippo通路蛋白的激活，并诱导YAP 1核定位，以增强YAP 1/TEAD的转录活性。总之，该研究表明，AGK不仅是Hippo-YAP 1通路的新靶点，而且还积极调节YAP 1表达，从而形成YAP 1-AGK正反馈环。
Acylglycerol kinase (AGK) uses adenosine triphosphate (ATP) and acylglycerol to generate adenosine diphosphate (ADP) and acyl‐sn‐glycerol 3‐phosphate in cells. Recent evidence has demonstrated that dysregulated AGK expression is associated with the development of various human cancers. This study investigated the effects of AGK on gastric cancer cell proliferation and carcinogenesis and explored the underlying molecular events. AGK expression was up‐regulated in gastric cancer and was associated with poor prognosis in gastric cancer patients. AGK overexpression increased gastric cancer proliferation, invasion capacity and the expression of the epithelial‐mesenchymal transition markers in vitro. Conversely, the knockdown of AGK expression reduced gastric cancer cell proliferation in vitro and in nude mouse tumour cell xenografts. Importantly, AGK expression was associated with the YAP1 expression in gastric cancer cells and tissues. YAP1 expression also transcriptionally induced AGK expression through the binding of TEAD to the AGK gene promoter. However, AGK expression inhibited the activation of the Hippo pathway proteins and induced YAP1 nuclear localization to enhance the transcription activity of YAP1/TEADs. In conclusion, the study demonstrates that AGK is not only a novel target of the Hippo‐YAP1 pathway, but that it also positively regulates YAP1 expression, thus forming a YAP1‐AGK–positive feedback loop.
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影响因子：
10.5
作者：
Meng Z;Moroishi T;Guan KL
通讯作者：
Guan KL
COX-2与YAP形成调节环促进肝癌细胞增殖和肿瘤发生
DOI：
10.1016/j.neo.2017.12.004
发表时间：
2018-04
期刊：
Neoplasia (New York, N.Y.)
影响因子：
--
作者：
Xu G;Wang Y;Li W;Cao Y;Xu J;Hu Z;Hao Y;Hu L;Sun Y
通讯作者：
Sun Y
一种产生溶血磷脂酸的新型酰基甘油激酶可调节前列腺癌细胞中与 EGFR 的串扰。
DOI：
10.1083/jcb.200407123
发表时间：
2005-06-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bektas M;Payne SG;Liu H;Goparaju S;Milstien S;Spiegel S
通讯作者：
Spiegel S
酰基甘油激酶通过抑制 FOXO1 转录因子促进乳腺癌细胞增殖和致瘤性
影响因子：
37.3
作者：
Wang X;Lin C;Zhao X;Liu A;Zhu J;Li X;Song L
通讯作者：
Song L
影响因子：
16
作者：
Vukotic, Milena;Nolte, Hendrik;Langer, Thomas
通讯作者：
Langer, Thomas