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TRIM59 predicts poor prognosis and promotes pancreatic cancer progression via the PI3K/AKT/mTOR-glycolysis signaling axis
被引:33
|作者:
Li, Rongkun
[1
]
Weng, Li
[1
]
Liu, Bingyan
[1
]
Zhu, Lili
[2
]
Zhang, Xiaoxin
[2
]
Tian, Guangang
[2
]
Hu, Lipeng
[2
]
Li, Qing
[2
]
Jiang, Shuheng
[2
]
Shang, Mingyi
[1
]
机构:
[1] Shanghai Jiao Tong Univ, Dept Intervent Radiol, Tongren Hosp, Sch Med, 1111 Xianxia Rd, Shanghai 200336, Peoples R China
[2] Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Shanghai Canc Inst, Renji Hosp,Sch Med, 800 Dongchuan Rd, Shanghai 200240, Peoples R China
关键词:
glycolysis;
metastasis;
pancreatic cancer;
PI3K;
AKT;
mTOR pathway;
proliferation;
tripartite motif containing 59;
TRIPARTITE MOTIF;
PATHWAY;
METABOLISM;
UBIQUITINATION;
ACTIVATION;
MIGRATION;
D O I:
10.1002/jcb.29433
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Aberrant expression of the tripartite motif containing 59 (TRIM59) has been reported to participate in the development and progression of various human cancers. However, its expression pattern and cellular roles in pancreatic cancer (PC) remains unclear. In our study, we found that TRIM59 expression was significantly increased in PC tissues and was positively correlated with several malignant behaviors and poor overall survival of PC patients based on bioinformatics analysis and immunohistochemistry staining. Functionally, small interfering RNA-mediated TRIM59 depletion inhibited cell proliferation and migration in vitro, while TRIM59 overexpression promoted cell proliferation and migration in vitro and drove tumor growth and liver metastasis in vivo. Mechanically, TRIM59 was found to enhance glycolysis through activating the PI3K/AKT/mTOR pathway, ultimately contributing to PC progression. Taken together, our results demonstrate that TRIM59 may be a potential predictor for PC and promotes PC progression via the PI3K/AKT/mTOR-glycolysis signaling pathway, which establishes the rationale for targeting the TRIM59-related pathways to treat PC.
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页码:1986 / 1997
页数:12
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