ERO1L promotes IL6/sIL6R signaling and regulates MUC16 expression to promote CA125 secretion and the metastasis of lung cancer cells.
ERO1L promotes IL6/sIL6R signaling and regulates MUC16 expression to promote CA125 secretion and the metastasis of lung cancer cells.
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ERO1L促进IL6/sIL6R信号传导并调节MUC16表达促进CA125分泌和肺癌细胞转移
DOI：
10.1038/s41419-020-03067-8
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发表时间：
2020-10-14
影响因子：
9
通讯作者：
He J
中科院分区：
文献类型：
--
作者：
Lei Y;Zang R;Lu Z;Zhang G;Huang J;Liu C;Wang Z;Mao S;Che Y;Wang X;Zheng S;Fang L;Sun N;He J
CA125是一种经典的肿瘤标志物，其异常分泌通常与各种肿瘤的预后不良有关。因此，本研究旨在探讨促进肺癌CA125分泌的可能机制。通过查询数据库，确定了基因内质网氧化还原酶1L(ERO1L)作为研究对象。用抗体芯片对肺癌细胞上清液进行筛选，发现最明显的分泌蛋白是CA125。ERO1L通过影响二硫键的形成促进IL6R的分泌。IL-6R与IL-6结合，触发了NF-κB信号通路的激活。然后，NF-κB与MUC16的启动子结合，导致MUC16的过表达。MUC16胞外片段被切割形成CA125，而MUC16的C末端促进EMT表型和IL6的释放，形成正反馈途径。综上所述，ERO1L可能通过IL6信号通路影响CA125的分泌，形成正反馈回路，进一步促进肺癌的发生发展。这可能扩大CA125在肺癌中的应用范围。
The abnormal secretion of CA125, a classic tumor marker, is usually related to a poor prognosis in various tumors. Thus, this study aimed to explore the potential mechanisms that promote CA125 secretion in lung cancer. By querying the database, the gene endoplasmic reticulum oxidoreductase 1L (ERO1L) was identified and chosen as the research subject. The antibody chips were used to screen the lung cancer cell supernatant and found that the most obvious secreted protein was CA125. ERO1L was found to promote the secretion of IL6R by affecting the formation of disulfide bonds. IL6R bound to IL6 and triggered the activation of the NF-κB signaling pathway. Then, NF-κB bound to the promoter of MUC16, resulting in overexpression of MUC16. The extracellular segment of MUC16 was cleaved to form CA125, while the C terminus of MUC16 promoted the EMT phenotype and the release of IL6, forming a positive feedback pathway. In conclusion, ERO1L might affect the secretion of CA125 through the IL6 signaling pathway and form a positive feedback loop to further promote the development of lung cancer. This might expand the application scope of CA125 in lung cancer.
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影响因子：
3.7
作者：
Aithal A;Junker WM;Kshirsagar P;Das S;Kaur S;Orzechowski C;Gautam SK;Jahan R;Sheinin YM;Lakshmanan I;Ponnusamy MP;Batra SK;Jain M
通讯作者：
Jain M
DOI：
10.1083/jcb.201506123
发表时间：
2015-10-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Konno T;Pinho Melo E;Lopes C;Mehmeti I;Lenzen S;Ron D;Avezov E
通讯作者：
Avezov E
影响因子：
3.8
作者：
Garg G;Gibbs J;Belt B;Powell MA;Mutch DG;Goedegebuure P;Collins L;Piwnica-Worms D;Hawkins WG;Spitzer D
通讯作者：
Spitzer D
影响因子：
--
作者：
Das S;Rachagani S;Torres-Gonzalez MP;Lakshmanan I;Majhi PD;Smith LM;Wagner KU;Batra SK
通讯作者：
Batra SK
DOI：
10.1098/rstb.2011.0403
发表时间：
2013-05-05
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Benham AM;van Lith M;Sitia R;Braakman I
通讯作者：
Braakman I