FUT2 Facilitates Autophagy and Suppresses Apoptosis via p53 and JNK Signaling in Lung Adenocarcinoma Cells.
FUT2 Facilitates Autophagy and Suppresses Apoptosis via p53 and JNK Signaling in Lung Adenocarcinoma Cells.
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作者：
肺癌是世界上最常见的癌症，发病率和死亡率都很高。我们前期研究表明，focusyltransferase 2 （FUT2）在肺腺癌（LUAD）中高表达，在LUAD的肿瘤发生过程中起着至关重要的作用。然而，其潜在的机制尚不完全清楚。自噬在癌症进展和转移过程中具有促进生存的作用，近年来引起了越来越多的关注。本研究发现，基于TCGA数据集，FUT2在肺腺癌中表达上调，曲线下面积（AUC）值为0.964。FUT2的下调减弱了自噬反应，LC3-II和Beclin1的降解证明了这一点。FUT2敲除后，AMPK、ULK1和PI3K III的磷酸化水平显著降低。FUT2促进p53从细胞质转位到细胞核，触发DRAM1通路，增强自噬。同时，FUT2的下调增加了JNK的磷酸化，促进了线粒体介导的细胞凋亡。FUT2的下调抑制了Z-VAD-FMK诱导的自噬，促进了雷帕霉素抑制的细胞凋亡。FUT2调控的自噬和凋亡相互拮抗。综上所述，这些发现提供了FUT2如何介导自噬和凋亡之间的串扰的机制理解，自噬和凋亡决定肺癌细胞的死亡和存活，导致肺腺癌的进展。
Lung cancer is the most common cancer with high morbidity and mortality worldwide. Our previous studies showed that fucosyltransferase 2 (FUT2) is highly expressed in lung adenocarcinoma (LUAD) and plays a vital role in the tumorigenesis of LUAD. However, the underlying mechanism is not fully understood. Autophagy has recently attracted increasing attention due to its pro-survival role in cancer progression and metastasis. Here, we found that FUT2 was up-regulated and had an AUC (Area Under Curve) value of 0.964 in lung adenocarcinoma based on the TCGA dataset. Knockdown of FUT2 weakened the autophagy response, as evidenced by a degradation of LC3-II and Beclin1. The phosphorylation levels of AMPK, ULK1, and PI3K III were significantly reduced by FUT2 knockdown. FUT2 promoted the translocation of p53 from the cytoplasm into the nucleus, which triggered the DRAM1 pathway and enhanced autophagy. Meanwhile, the knockdown of FUT2 increased the phosphorylation of JNK and promoted mitochondrial-mediated apoptosis. Furthermore, the knockdown of FUT2 inhibited the autophagy induced by Z-VAD-FMK and promoted the apoptosis suppressed by rapamycin. The autophagy and apoptosis regulated by FUT2 antagonized each other. Taken together, these findings provide a mechanistic understanding of how FUT2 mediated the crosstalk between autophagy and apoptosis, which determine lung cancer cell death and survival, leading to the progression of lung adenocarcinoma.
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影响因子：
10.5
作者：
Ruan HB;Ma Y;Torres S;Zhang B;Feriod C;Heck RM;Qian K;Fu M;Li X;Nathanson MH;Bennett AM;Nie Y;Ehrlich BE;Yang X
通讯作者：
Yang X
影响因子：
21.3
作者：
通讯作者：
--
岩藻糖基转移酶 2 通过 TGF-β Smad 信号通路诱导肺腺癌上皮间质转化
影响因子：
3.7
作者：
Deng, Guoqing;Chen, Lvao;Chen, Xiaoming
通讯作者：
Chen, Xiaoming
DOI：
10.1038/nrm3735
发表时间：
2014-02
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.6
作者：
Fahie K;Zachara NE
通讯作者：
Zachara NE