Protein tyrosine phosphatase PTP4A1 promotes proliferation and
epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma via the
PI3K/AKT pathway
#MMPMID27655691
Liu LZ
; He YZ
; Dong PP
; Ma LJ
; Wang ZC
; Liu XY
; Duan M
; Yang LX
; Shi JY
; Zhou J
; Fan J
; Gao Q
; Wang XY
Oncotarget
2016[Nov]; 7
(46
): 75210-75220
PMID27655691
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The protein tyrosine phosphatase PTP4A1 is a key molecule that activates tyrosine
phosphorylation, which is important for cancer progression and metastasis.
However, the clinical implications and biological function of PTP4A1 in
intrahepatic cholangiocarcinoma (ICC) remains unknown. Here, we showed that
PTP4A1 was frequently overexpressed in ICC versus adjacent non-tumor tissues.
This overexpression significantly correlated with aggressive tumor
characteristics like the presence of lymph node metastasis and advanced tumor
stages. Survival analysis further indicated that high PTP4A1 expression was
significantly and independently associated with worse survival and increased
recurrence in ICC patients. Moreover, through forced overexpression and
knock-down of PTPT4A1, we demonstrated that PTP4A1 could significantly promote
ICC cells proliferation, colony formation, migration, and invasion in vitro, and
markedly enhance tumor progression in vivo. Mechanistically, PTP4A1 was involved
in PI3K/AKT signaling and its downstream molecules, such as phosphorylation level
of GSK3? and up-regulation of CyclinD1, in ICC cells to promote proliferation.
Importantly, PTP4A1 induced ICC cells invasion was through activating PI3K/AKT
signaling controlled epithelial-mesenchymal transition (EMT) process by
up-regulating Zeb1 and Snail. Thus, PTP4A1 may serve as a potential oncogene that
was a valuable prognostic biomarker and therapeutic target for ICC.
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