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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Exp+Clin+Cancer+Res
2017 ; 36
(1
): 84
Nephropedia Template TP
gab.com Text
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English Wikipedia
High expression of Collagen Triple Helix Repeat Containing 1 (CTHRC1) facilitates
progression of oesophageal squamous cell carcinoma through MAPK/MEK/ERK/FRA-1
activation
#MMPMID28645305
Wang C
; Li Z
; Shao F
; Yang X
; Feng X
; Shi S
; Gao Y
; He J
J Exp Clin Cancer Res
2017[Jun]; 36
(1
): 84
PMID28645305
show ga
BACKGROUND: Oesophageal cancer is one of the most common malignancies
worldwide,and oesophageal squamous cell carcinoma (ESCC) is the predominant
histological type both globally and in China. Collagen triple helix repeat
containing 1 (CTHRC1) has been found to be upregulated in ESCC. However, its role
in tumourigenesis and progression of ESCC remains unclear. METHODS: Using our
previous ESCC mRNA profiling data, we screened upregulated genes to identify
those required for proliferation. Immunohistochemistry was performed to determine
the level of CTHRC1 protein expression in 204 ESCC patients. Correlations between
CTHRC1 expression and clinicopathological characteristics were assessed. In
addition, pyrosequencing and 5-aza-dC treatment were performed to evaluate
methylation status of CTHRC1 promoter. In vitro and in vivo analyses were also
conducted to determine the role of CTHRC1 in ESCC cell proliferation, migration
and invasion, and RNA sequencing and molecular experiments were performed to
study the underlying mechanisms. RESULTS: Based on mRNA profiling data, CTHRC1
was identified as one of the most significantly upregulated genes in ESCC tissues
(n?=?119, fold change?=?20.5, P?=?2.12E-66). RNA interference screening also
showed that CTHRC1 was required for cell proliferation. Immunohistochemistry
confirmed markedly high CTHRC1 protein expression in tumour tissues, and high
CTHRC1 expression was positively correlated with advanced T stage (P?=?0.043),
lymph node metastasis (P?=?0.023), TNM stage (P?=?0.024) and poor overall
survival (P?=?0.020). Promoter hypomethylation at cg07757887 may contribute to
increased CTHRC1 expression in ESCC cells and tumours. Forced overexpression of
CTHRC1 significantly enhanced cell proliferation, migration and invasion, whereas
depletion of CTHRC1 suppressed these cellular functions in three ESCC cell lines
and xenografts. CTHRC1 was found to activate FRA-1 (Fos-related antigen 1, also
known as FOSL1) through the MAPK/MEK/ERK cascade, which led to upregulation of
cyclin D1 and thus promoted cell proliferation. FRA-1 also induced
snail1-mediated MMP14 (matrix metallopeptidase 14, also known as MT1-MMP)
expression to facilitate ESCC cell invasion, migration, and metastasis.
CONCLUSIONS: Our data suggest that CTHRC1 may act as an oncogenic driver in
progression and metastasis of ESCC, and may serve as a potential biomarker for
prognosis and personalized therapy.