The deubiquitinase USP9X promotes tumor cell survival and confers chemoresistance through YAP1 stabilization.
The deubiquitinase USP9X promotes tumor cell survival and confers chemoresistance through YAP1 stabilization.
复制标题
去泛素酶 USP9X 促进肿瘤细胞存活，并通过稳定 YAP1 赋予化疗耐药性。
DOI：
10.1038/s41388-018-0134-2
复制
发表时间：
2018-05
期刊：
影响因子：
8
通讯作者：
Yuan J
中科院分区：
文献类型：
--
作者：
Li L;Liu T;Li Y;Wu C;Luo K;Yin Y;Chen Y;Nowsheen S;Wu J;Lou Z;Yuan J
是相关蛋白1（YAP 1），一个主要的下游效应的Hippo途径，作为一个转录调节因子的功能，并在细胞控制器官大小和肿瘤生长的重要作用。已经在不同类型的人类癌症中阐明了YAP 1的致癌活性升高，这有助于癌细胞存活和化学抗性。然而，YAP 1在癌症中过表达的分子机制仍然不清楚。在这里，我们证明了去泛素化酶USP 9 X去泛素化并稳定YAP 1，从而促进癌细胞存活。USP 9 X表达增加与人乳腺癌细胞系和患者样本中YAP 1蛋白增加相关。此外，USP 9 X的消耗增加了YAP 1聚泛素化，这反过来又提高了YAP 1的周转率和细胞对化疗的敏感性。总体而言，我们的研究确立了USP 9 X-YAP 1轴作为乳腺癌的重要调节机制，并为乳腺癌治疗中的潜在治疗干预提供了理论基础。
The Yes-associated protein 1 (YAP1), a major downstream effector of the Hippo pathway, functions as a transcriptional regulator and has an important role in cellular control of organ size and tumor growth. Elevated oncogenic activity of YAP1 has been clarified in different types of human cancers, which contributes to cancer cell survival and chemoresistance. However, the molecular mechanism of YAP1 overexpression in cancer is still not clear. Here we demonstrate that the deubiquitination enzyme USP9X deubiquitinates and stabilizes YAP1, thereby promoting cancer cell survival. Increased USP9X expression correlates with increased YAP1 protein in human breast cancer cell lines and patient samples. Moreover, depletion of USP9X increases YAP1 polyubiquitination, which in turn elevates YAP1 turnover and cell sensitivity to chemotherapy. Overall, our study establishes the USP9X-YAP1 axis as an important regulatory mechanism of breast cancer and provides a rationale for potential therapeutic interventions in the treatment of breast cancer.
登录
查看更多内容
DOI：
10.1002/stem.2283
发表时间：
2016-05
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Jung KH;McCarthy RL;Zhou C;Uprety N;Barton MC;Beretta L
通讯作者：
Beretta L
影响因子：
64.5
作者：
Rosenbluh J;Nijhawan D;Cox AG;Li X;Neal JT;Schafer EJ;Zack TI;Wang X;Tsherniak A;Schinzel AC;Shao DD;Schumacher SE;Weir BA;Vazquez F;Cowley GS;Root DE;Mesirov JP;Beroukhim R;Kuo CJ;Goessling W;Hahn WC
通讯作者：
Hahn WC
影响因子：
3.7
作者：
Nguyen HT;Kugler JM;Cohen SM
通讯作者：
Cohen SM
影响因子：
7.7
作者：
Kim, Miju;Kim, Minchul;Lim, Dae-Sik
通讯作者：
Lim, Dae-Sik
影响因子：
64.5
作者：
Dupont, Sirio;Mamidi, Anant;Piccolo, Stefano
通讯作者：
Piccolo, Stefano