Protein tyrosine phosphatase PTP4A1 promotes proliferation and epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma via the PI3K/AKT pathway

被引:37
作者
Liu, Long-Zi [1 ,2 ]
He, Yi-Zhou [3 ]
Dong, Ping-Ping [4 ]
Ma, Li-Jie [1 ,2 ]
Wang, Zhi-Chao [1 ,2 ]
Liu, Xin-Yang [5 ,6 ]
Duan, Meng [1 ,2 ]
Yang, Liu-Xiao [1 ,2 ]
Shi, Jie-Yi [1 ,2 ]
Zhou, Jian [1 ,2 ]
Fan, Jia [1 ,2 ]
Gao, Qiang [1 ,2 ]
Wang, Xiao-Ying [1 ,2 ]
机构
[1] Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Shanghai 200032, Peoples R China
[2] Fudan Univ, Minist Educ, Key Lab Carcinogenesis & Canc Invas, Shanghai 200032, Peoples R China
[3] Fudan Univ, Zhongshan Hosp, Dept Crit Care Med, Shanghai 200032, Peoples R China
[4] Fudan Univ, Shanghai Inst Liver Dis, Zhongshan Hosp, Dept Gastroenterol & Hepatol, Shanghai 200032, Peoples R China
[5] Fudan Univ, Shanghai Canc Ctr, Dept Med Oncol, Shanghai 200032, Peoples R China
[6] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China
基金
中国国家自然科学基金;
关键词
PTP4A1; intrahepatic cholangiocarcinoma; prognosis; oncogene; epithelial-mesenchymal transition; HEPATOCELLULAR-CARCINOMA; REGENERATING LIVER; CELL-PROLIFERATION; GROWTH; CANCER; MIGRATION; INVASION; PATHOGENESIS; EXPRESSION; PRL-1;
D O I
10.18632/oncotarget.12116
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 beta 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.
引用
收藏
页码:75210 / 75220
页数:11
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