<br>YDJC 通过 PP2A 泛素化逃避与 CDC16 的相互作用，从而诱导上皮间质转化。,Journal of Oncology

当前位置： X-MOL 学术 › J. Oncol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

YDJC 通过 PP2A 泛素化逃避与 CDC16 的相互作用，从而诱导上皮间质转化。
Journal of Oncology Pub Date : 2019-08-07 , DOI: 10.1155/2019/3542537
Eun Ji Kim ₁ , Mi Kyung Park ₂ , Gyeoung-Jin Kang ₁ , Hyun Jung Byun ₁ , Hyun Ji Kim ₁ , Lu Yu ₁ , Boram Kim ₁ , Hee-Sung Chae ₁ , Young-Won Chin ₁ , Jae Gal Shim ₂ , Ho Lee ₂ , Chang Hoon Lee ₁

Affiliation

肺癌是世界上癌症相关死亡的第一大原因。需要适当的肺癌诊断标志物和新靶点。壳寡糖脱乙酰酶同系物 (YDJC) 催化乙酰化碳水化合物的脱乙酰化；然而，YDJC 在肺癌进展中的作用仍有待研究。采用A549肺癌原位小鼠模型进行小鼠实验。我们发现，在原位小鼠模型中，YDJC 过度表达有助于肺癌进展。长期治疗（48小时）会在鞘氨醇磷酸胆碱（SPC）诱导的上皮间质转化（EMT）中诱导YDJC表达。在 SPC 诱导的 EMT 中，YDJC (siYDJC) 基因沉默可减少 N-钙粘蛋白表达并增加 E-钙粘蛋白表达。 YDJC 的过表达可以逆转它们，但脱乙酰酶缺陷突变体的过表达则不能。有趣的是，YDJC 结合伴侣 CDC16 的过度表达会抑制 EMT。 ERK2 在 siCDC16 诱导的 EMT 中被激活。 YDJC 过表达会降低蛋白磷酸酶 2A (PP2A) 的表达，而 CDC16 过表达会诱导 PP2A 表达。 YDJC 过表达可诱导 PP2A 泛素化，但不能。 CDC16 过表达增加了 YDJC 的泛素化。这些结果表明，YDJC 通过诱导 PP2A 泛素化来增强 EMT，从而促进肺癌的进展。因此，YDJC可能成为肺癌抗肿瘤治疗的新靶点。

"点击查看英文标题和摘要"

YDJC Induces Epithelial-Mesenchymal Transition via Escaping from Interaction with CDC16 through Ubiquitination of PP2A.

Lung cancer is the number 1 cause of cancer-related casualties in the world. Appropriate diagnostic markers and novel targets for lung cancer are needed. Chitooligosaccharide deacetylase homolog (YDJC) catalyzes the deacetylation of acetylated carbohydrates; however, the role of YDJC in lung cancer progression has yet to be studied. A549 lung cancer orthotopic mouse model was used for mice experiments. We found that YDJC overexpression contributes to lung cancer progression in an orthotopic mouse model. Long-term treatment (48 h) induces YDJC expression in sphingosylphosphorylcholine (SPC)-induced epithelial-mesenchymal transition (EMT). Gene silencing of YDJC (siYDJC) reduced N-cadherin expression and increased E-cadherin expression in SPC-induced EMT. Overexpression of YDJC reverses them but overexpression of the deacetylase deficient mutant could not. Interestingly, overexpression of CDC16, a YDJC binding partner, suppressed EMT. ERK2 is activated in siCDC16-induced EMT. YDJC overexpression reduces expression of protein phosphatase 2A (PP2A), whereas CDC16 overexpression induces PP2A expression. YDJC overexpression induced ubiquitination of PP2A but could not. CDC16 overexpression increased the ubiquitination of YDJC. These results suggest that YDJC contributes to the progression of lung cancer via enhancing EMT by inducing the ubiquitination of PP2A. Therefore, YDJC might be a new target for antitumor therapy against lung cancer.

更新日期：2019-08-07

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南