Tankyrase Promotes Aerobic Glycolysis and Proliferation of Ovarian Cancer through Activation of Wnt/-Catenin Signaling

被引:33
作者
Yang, Hong-Yi [1 ]
Shen, Jin-Xing [2 ]
Wang, Yi [2 ]
Liu, Yu [2 ]
Shen, Dong-Yan [2 ]
Quan, Song [1 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Dept Obstet & Gynecol, Ctr Reprod Med, Guangzhou 510515, Guangdong, Peoples R China
[2] Xiamen Univ, Sch Med, Affiliated Hosp 1, Dept Biobank, Xiamen 361003, Peoples R China
基金
中国国家自然科学基金;
关键词
PYRUVATE-CARBOXYLASE; KAPPA-B; INHIBITION; GROWTH; PATHWAY; CELLS; CHEMOSENSITIVITY; TARGET;
D O I
10.1155/2019/2686340
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Tankyrase (TNKS) plays important roles in the malignancy of several cancers such as human lung tumor, breast cancer, and hepatocellular cancer. However, its exact functions and molecular mechanisms in ovarian cancer remain unclear. In this study, we found that TNKS was aberrantly overexpressed in human ovarian cancer tissues and associated with poor patient prognosis. TNKS inhibition or knockdown not only reduced ovarian cancer cell proliferation, colony formation, migration, invasion, and tumorigenic potential in nude mice but also enhanced the drug susceptibility of ovarian cancer cells through arresting cell cycle and inducing apoptosis. These phenotypic changes correlated with downregulation of targets (Cyclin D1, MDR, and MMP-9) of Wnt/-catenin signaling. Furthermore, downregulation of TNKS suppressed the glucose uptake, lactate excretion, and cellular ATP levels and increased cellular O-2 consumption rates. Molecular mechanism studies revealed that TNKS promoted aerobic glycolysis at least in part due to upregulation of pyruvate carboxylase (PC) via activation of Wnt/-catenin/snail signaling. In agreement with these findings, expression of TNKS is positively associated with snail and PC in clinical ovarian cancer samples. Our findings identified TNKS as an oncogenic regulator of ovarian cancer cells proliferation that promotes aerobic glycolysis via activation of Wnt/-catenin signaling, indicating that the TNKS might serve as a potential molecular target for clinical therapy of Wnt/-catenin dependent ovarian cancer.
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页数:14
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