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岩藻糖基化的CD147增强上皮性卵巢癌细胞的自噬。

The fucosylated CD147 enhances the autophagy in epithelial ovarian cancer cells.

作者信息

Hu Zhenhua, Cai Mingbo, Deng Lu, Zhu Liancheng, Gao Jian, Tan Mingzi, Liu Juanjuan, Lin Bei

机构信息

Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning, 110004, China.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.

出版信息

Oncotarget. 2016 Dec 13;7(50):82921-82932. doi: 10.18632/oncotarget.13289.

Abstract

Autophagy is modulated by multiple factors including CD147, but little is know about the effects and mechanism by which the modification of CD147 by Lewis y antigen regulates autophagy of ovarian cancer cell. Here, we reported that Lewis y antigen can promote basic autophagy activity and restrain autophagic cell death in ovarian cancer cells. Furthermore, human whole genome expression profile microarrays and massage pathway analysis revealed that during early stages of autophagy in ovarian cancer cells with highly expressing Lewis y antigen, PI3K/Akt-mTOR activity was reduced, in contrast, the PI3K/Akt-mTOR signaling pathway was activated as the length of amino acid deprivation increased, which inhibited eIF4G2 expression, further decreased the transcription of autophagy-related genes, suppressed autophagic cell death. we also elaborated that co-regulates protein degradation in cells via the ubiquitin-proteasome system and the autophagy-lysosome pathway. These findings suggested that the modification of CD147 by Lewis y antigen enhanced the survival ability by promoting basic autophagy activity and restraining autophagic cell death in ovarian cancer , thus playing an important role in ovarian cancer malignant progression.

摘要

自噬受多种因素调节,包括CD147,但关于Lewis y抗原修饰CD147调节卵巢癌细胞自噬的作用及机制知之甚少。在此,我们报道Lewis y抗原可促进卵巢癌细胞的基础自噬活性并抑制自噬性细胞死亡。此外,人类全基因组表达谱微阵列和信号通路分析显示,在高表达Lewis y抗原的卵巢癌细胞自噬早期阶段,PI3K/Akt-mTOR活性降低,相反,随着氨基酸剥夺时间延长,PI3K/Akt-mTOR信号通路被激活,抑制了eIF4G2表达,进一步降低自噬相关基因的转录,抑制自噬性细胞死亡。我们还阐述了其通过泛素-蛋白酶体系统和自噬-溶酶体途径共同调节细胞内蛋白质降解。这些发现表明,Lewis y抗原修饰CD147通过促进基础自噬活性和抑制卵巢癌细胞的自噬性细胞死亡增强了生存能力,从而在卵巢癌恶性进展中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca9/5347741/961ba3a083ca/oncotarget-07-82921-g001.jpg

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