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SOX9通过Hippo-YAP信号通路促进胃癌细胞的上皮-间质转化。

SOX9 promotes epithelial-mesenchymal transition via the Hippo-YAP signaling pathway in gastric carcinoma cells.

作者信息

Zhou Hailang, Li Guiqin, Huang Shu, Feng Yadong, Zhou Aijun

机构信息

Department of Gastroenterology, Medical Center for Digestive Diseases, People's Hospital of Lianshui, Huaian, Jiangsu 223400, P.R. China.

Department of Gastroenterology, Medical Center for Digestive Diseases, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.

出版信息

Oncol Lett. 2019 Jul;18(1):599-608. doi: 10.3892/ol.2019.10387. Epub 2019 May 21.

Abstract

SRY-box 9 (SOX9) is overexpressed in a number of human tumors, including gastric cancer (GC). However, the function of SOX9 in the development of GC remains unknown. In the present study, SOX9 activated the Hippo-yes-associated protein (YAP) signaling pathway to enhance the epithelial-mesenchymal transition in GC cell lines. The results suggested that SOX9 knockdown inhibited invasion, proliferation and migration of GC cells. Furthermore, SOX9 silencing upregulated the expression of E-cadherin, an epithelial marker, and downregulated the expression of mesenchymal markers, including snail family transcriptional repressor 1, vimentin and N-cadherin. SOX9 overexpression increased the expression of the aforementioned markers. SOX9 significantly affected YAP phosphorylation and total YAP protein levels, suggesting that SOX9 is involved in the Hippo-YAP signaling pathway. The current study revealed that SOX9 may be involved in the pathogenesis of GC, and further elucidation of the pathways involved may support the development of novel therapeutic options for the treatment of GC.

摘要

SRY 盒 9(SOX9)在包括胃癌(GC)在内的多种人类肿瘤中过表达。然而,SOX9 在 GC 发生发展中的功能尚不清楚。在本研究中,SOX9 激活了 Hippo - Yes 相关蛋白(YAP)信号通路,以增强 GC 细胞系中的上皮 - 间质转化。结果表明,敲低 SOX9 可抑制 GC 细胞的侵袭、增殖和迁移。此外,SOX9 沉默上调了上皮标志物 E - 钙黏蛋白的表达,并下调了包括蜗牛家族转录抑制因子 1、波形蛋白和 N - 钙黏蛋白在内的间质标志物的表达。SOX9 过表达增加了上述标志物的表达。SOX9 显著影响 YAP 的磷酸化和总 YAP 蛋白水平,表明 SOX9 参与了 Hippo - YAP 信号通路。当前研究表明,SOX9 可能参与 GC 的发病机制,进一步阐明相关通路可能有助于开发治疗 GC 的新型治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e6/6546990/da01d5a895e3/ol-18-01-0599-g00.jpg

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