title: Hes1 triggers epithelial-mesenchymal transition (EMT)-like cellular marker alterations and promotes invasion and metastasis of nasopharyngeal carcinoma by activating the PTEN/AKT pathway.
abstract: 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.
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.|Department of Pathology, Guangdong Medical University, Dongguan 523808, China.
authors.forename: Sheng-Chun
authors.initials: SC
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Lin
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Hui-Yan
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Qin
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jun-Shuang
authors.initials: JS
authors.lastname: Jia
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Hong-Fen
authors.initials: HF
authors.lastname: Shen
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Rao-Ying
authors.initials: RY
authors.lastname: Xie
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wei
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.|Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Oncology, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China.
authors.forename: Xiao-Xiang
authors.initials: XX
authors.lastname: Rong
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Zhao
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhang
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jun-Wen
authors.initials: JW
authors.lastname: Shi
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Kai-Tai
authors.initials: KT
authors.lastname: Yao
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.
authors.forename: Wei-Ren
authors.initials: WR
authors.lastname: Luo
authors.affiliation: Joint Program in Transfusion Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Cancer Research Institute, Southern Medical University, Guangzhou 510515, China.|Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Xiao
mesh_terms: D000818:Animals; D002277:Carcinoma; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D000072056:Transcription Factor HES-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000072056:Transcription Factor HES-1; C078493:HES1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Hes1; PTEN; cancer invasion and metastasis; epithelial-mesenchymal transition (EMT); nasopharyngeal carcinoma (NPC)