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YAP1 过表达与乳腺癌患者预后不良相关,并通过抑制 PTEN 诱导乳腺癌细胞生长。

YAP1 overexpression is associated with poor prognosis of breast cancer patients and induces breast cancer cell growth by inhibiting PTEN.

机构信息

Department of Interventional Radiology Zhejiang Cancer Hospital Hangzhou China.

出版信息

FEBS Open Bio. 2019 Feb 14;9(3):437-445. doi: 10.1002/2211-5463.12597. eCollection 2019 Mar.

Abstract

YES-associated protein 1 (YAP1) plays a key role as a transcriptional coactivator in the Hippo tumor suppressor pathway. YAP1 is overexpressed in a variety of cancers and is considered to be encoded by a proto-oncogene. However, the role of YAP1 remains debatable, because both gain and loss of YAP1 expression have both been reported in breast cancer (BC). Here, we found that elevated expression of YAP1 mRNA in BC was negatively correlated with relapse-free, distant metastases-free and overall survival rates. We then knocked down or overexpressed YAP1 in human BC cells, and examined cell proliferation, apoptosis, and tumorigenic ability . We identified that YAP1 promotes cell growth and inhibits cell apoptosis of BC through the phosphatase and tensin homolog deleted on chromosome 10-AKT signaling pathway, and thus suggest that YAP1 might serve as a new target for inhibiting BC progression.

摘要

YES 相关蛋白 1(YAP1)作为 Hippo 肿瘤抑制通路中的转录共激活因子发挥着关键作用。YAP1 在多种癌症中过度表达,被认为是原癌基因编码的。然而,YAP1 的作用仍然存在争议,因为在乳腺癌(BC)中既报道了 YAP1 表达的增加,也报道了 YAP1 表达的减少。在这里,我们发现 BC 中 YAP1 mRNA 的高表达与无复发生存率、无远处转移生存率和总生存率呈负相关。然后,我们在人 BC 细胞中敲低或过表达 YAP1,并检测细胞增殖、凋亡和致瘤能力。我们发现 YAP1 通过磷酸酶和张力蛋白同源物缺失于染色体 10-AKT 信号通路促进 BC 细胞的生长并抑制细胞凋亡,因此提示 YAP1 可能作为抑制 BC 进展的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc60/6396162/52351394456d/FEB4-9-437-g001.jpg

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