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2015 ; 6
(34
): 36713-30
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Hes1 triggers epithelial-mesenchymal transition (EMT)-like cellular marker
alterations and promotes invasion and metastasis of nasopharyngeal carcinoma by
activating the PTEN/AKT pathway
#MMPMID26452025
Wang SC
; Lin XL
; Wang HY
; Qin YJ
; Chen L
; Li J
; Jia JS
; Shen HF
; Yang S
; Xie RY
; Wei F
; Gao F
; Rong XX
; Yang J
; Zhao WT
; Zhang TT
; Shi JW
; Yao KT
; Luo WR
; Sun Y
; Xiao D
Oncotarget
2015[Nov]; 6
(34
): 36713-30
PMID26452025
show ga
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.