Fructose-1,6-bisphosphatase is a novel regulator of Wnt/β-Catenin pathway in breast cancer

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• 作者：Kaichun Li^a ; Mingzhen Ying^a ; Dan Feng^a ; Jie Du^b ; Shiyu Chen^b ; Bing Dan^b ; Cuihua Wang^b ; Yajie Wang^a ; ^{shtumor@163.com}
• 关键词：FBP1 ; Oncomine ; GSEA ; Wnt/βbeta ; -Catenin pathway ; Breast cancer
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：84
• 期：Complete
• 页码：1144-1149
• 全文大小：2072 K
• 卷排序：84

文摘

Fructose-1,6-bisphosphatase (FBP1), the rate-limiting enzyme in gluconeogenesis, is a tumor suppressor that frequently down-regulated in cancers, especially breast cancer. Here, we provide both supporting and contradicting evidences about the expression pattern and function of FBP1 in breast cancer. Data mining of Oncomine database showed that FBP1 is commonly up-regulated in tumor tissues compared with non-tumor tissues regardless of histological type. Analysis of a large-scale cohort derived from Kaplan-Meier Plotter showed that lower FBP1 expression associated with poor clinical outcome. Genetic silencing of FBP1 reduced aerobic glycolysis and the malignant potential of breast cancer cells. Gene set enrichment analysis (GSEA) of the expression profiles of breast cancer cells (n = 59) revealed that cells exhibiting high expression of FBP1 had a lower activity of Wnt/β-Catenin pathway. FBP1 down-regulation enhanced the activity of Wnt/β-Catenin pathway and increased the level of its downstream targets, including c-Myc and MMP7. Collectively, our findings indicate that elevated FBP1 is a critical modulator in breast cancer progression by altering glucose metabolism and the activity of Wnt/β-Catenin pathway.