Abstract
BackgroundEmerging evidence shows that Hippo signal pathways can regulate the progression of various cancer. While the roles of Yes-associated protein (YAP), the key transducer of Hippo signals, in the development of endometrial cancer (EC) are rarely investigated.MethodsThe expression of YAP in endometrial cancer cells and tissues was measured. Its roles in proliferation and expression of interleukins (ILs) were investigated by use of its specific siRNA or inhibitor (verteporfin, VP).ResultsYAP was upregulated in endometrial cancer cells and tissues. Knockdown of YAP or VP can suppress the proliferation while increase its chemo-sensitivity of EC cells. We found that targeted inhibition of YAP can decrease the expression of interleukin-6 (IL-6) and IL-11 in EC cells. Recombinant IL-6 or IL-11 can attenuate si-YAP suppressed proliferation of EC cells. Chromatin immunoprecipitation (ChIP) assay suggested that YAP can directly bind with the promoter of IL-6 and induce its transcription. As to IL-11, inhibitor of NF-κB (BAY 11–7082) can significantly down regulate the mRNA expression of IL-11. Over expression of p65 abolished si-YAP suppressed transcription of IL-11. It suggested that NF-κB was involved in the YAP regulated expression of IL-11.ConclusionsYAP can regulate the proliferation and progression of EC cells. It suggested that targeted inhibition of YAP might be a potent potential approach for EC therapy.
Highlights
Endometrial cancer (EC) is the most common gynecological cancer in developed countries (Dizon, 2010), with about 50,327 deaths occurring worldwide each year (Siegel et al, 2016)
The expression of Yes-associated protein (YAP) is upregulated in endometrial cancer (EC) cells and tissues Firstly, the expression of YAP was measured in various EC cells and the human endometrial cell line endometrial stromal cell (ESC)
We further evaluated the expression of YAP in seven collected human EC tissues and the paired normal adjacent tissues
Summary
Endometrial cancer (EC) is the most common gynecological cancer in developed countries (Dizon, 2010), with about 50,327 deaths occurring worldwide each year (Siegel et al, 2016). For EC patients with metastasis, treatment failure is still high due to the loss of opportunity for surgery. In advance stages of EC patients, the growth and systemic metastasis lead. As the key downstream effector in the Hippo signaling cascade, the Yes-associated protein (YAP) is a major contributor to cancer pathophysiology (Pan, 2010; Zhao et al, 2007). After activation of Hippo signals, MST1/2 is phosphorylated and activates LATS1/2 (Real et al, 2018). While the roles of Yes-associated protein (YAP), the key transducer of Hippo signals, in the development of endometrial cancer (EC) are rarely investigated
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