Hes1 triggers epithelial-mesenchymal transition (EMT)-like cellular marker alterations and promotes invasion and metastasis of nasopharyngeal carcinoma by activating the PTEN/AKT pathway.
机构：[1]Cancer Research Institute, Southern Medical University, Guangzhou 510515, China[2]Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China[3]Joint Program in Transfusion Medicine, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA[4]Department of Pathology, Guangdong Medical University, Dongguan 523808, China[5]Department of Oncology, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China[6]Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China
Overexpression of the transcriptional factor Hes1 (hairy and enhancer of split-1) has been observed in numerous cancers, but the precise roles of Hes1 in epithelial-mesenchymal transition (EMT), cancer invasion and metastasis remain unknown. Our current study firstly revealed that Hes1 upregulation in a cohort of human nasopharyngeal carcinoma (NPC) biopsies is significantly associated with the EMT, invasive and metastatic phenotypes of cancer. In the present study, we found that Hes1 overexpression triggered EMT-like cellular marker alterations of NPC cells, whereas knockdown of Hes1 through shRNA reversed the EMT-like phenotypes, as strongly supported by Hes1-mediated EMT in NPC clinical specimens described above. Gain-of-function and loss-of-function experiments demonstrated that Hes1 promoted the migration and invasion of NPC cells in vitro. In addition, exogenous expression of Hes1 significantly enhanced the metastatic ability of NPC cells in vivo. Chromatin immunoprecipitation (ChIP) assays showed that Hes1 inhibited PTEN expression in NPC cells through binding to PTEN promoter region. Increased Hes1 expression and decreased PTEN expression were also observed in a cohort of NPC biopsies. Additional studies demonstrated that Hes1-induced EMT-like molecular changes and increased motility and invasion of NPC cells were mediated by PTEN. Taken together, our results suggest, for what we believe is the first time, that Hes1 plays an important role in the invasion and metastasis of NPC through inhibiting PTEN expression to trigger EMT-like phenotypes.
基金：
This work was supported by the National Natural Science Foundation of China (Grant No. 81172587 and 81372896, to D. Xiao; Grant No. 81560441, to S.-J. Xiao; Grant No. 31271042, to J.-Z. Li; Grant No. 61427807), the Natural Science Foundation of Guangdong Province of China (Grant No. 2014A030313294 to D. Xiao; Grant No. 9151063101000015, to J.-S. Jia), the Science and Technology Planning Project of Guangdong Province of China (Grant No. 2009B060300008 and 2013B060300013, to D. Xiao; Grant No. 2012B061700099, to J.-Z. Li), the China Postdoctoral Science Foundation (Grant No. 2015M572338, to X.-L. Lin), the National High Technology Research and Development Program of China (Program 863) (Grant No. 2012AA02A501), the Ministry of Science and Technology National Basic Research Program of China (973 program) (Grant No. 2011CBA01006, to W.-W. Gu), the Medical Scientific Research Foundation of Guangdong Province of China (Grant No. A2015105, to S.-C. Wang; Grant No. B2014238, to H.F. Shen), the Scientific and Technological Personnel Training Program for Young Scientists, Scientific Research Starting Foundation of Southern Medical University (Grant No. B1012108, to H.F. Shen) and the Introduced Major Research and Development Project Funded by Fujian Province (Grant No. 2012I2014).
语种：
外文
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出版当年[2014]版：
大类|2 区医学
小类|2 区肿瘤学3 区细胞生物学
最新[2025]版：
无
第一作者：
第一作者机构：[1]Cancer Research Institute, Southern Medical University, Guangzhou 510515, China[4]Department of Pathology, Guangdong Medical University, Dongguan 523808, China
共同第一作者：
通讯作者：
通讯机构：[1]Cancer Research Institute, Southern Medical University, Guangzhou 510515, China[2]Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China
推荐引用方式(GB/T 7714)：
Sheng-Chun Wang,Xiao-Lin Lin,Hui-Yan Wang,et al.Hes1 triggers epithelial-mesenchymal transition (EMT)-like cellular marker alterations and promotes invasion and metastasis of nasopharyngeal carcinoma by activating the PTEN/AKT pathway.[J].Oncotarget.2015,6(34):36713-30.doi:10.18632/oncotarget.5457.
APA：
Sheng-Chun Wang,Xiao-Lin Lin,Hui-Yan Wang,Yu-Juan Qin,Lin Chen...&Dong Xiao.(2015).Hes1 triggers epithelial-mesenchymal transition (EMT)-like cellular marker alterations and promotes invasion and metastasis of nasopharyngeal carcinoma by activating the PTEN/AKT pathway..Oncotarget,6,(34)
MLA：
Sheng-Chun Wang,et al."Hes1 triggers epithelial-mesenchymal transition (EMT)-like cellular marker alterations and promotes invasion and metastasis of nasopharyngeal carcinoma by activating the PTEN/AKT pathway.".Oncotarget 6..34(2015):36713-30
