title: Fructose-1,6-bisphosphatase is a novel regulator of Wnt/β-Catenin pathway in breast cancer.
abstract: 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.
authors: Department of Oncology, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, PR China.
authors: Kaichun
authors: K
authors: Li
authors: Department of Oncology, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, PR China.
authors: Mingzhen
authors: M
authors: Ying
authors: Department of Oncology, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, PR China.
authors: Dan
authors: D
authors: Feng
authors: Department of Oncology, Tianyou Hospital Affiliated to Tongji University, Shanghai 200331, PR China.
authors: Jie
authors: J
authors: Du
authors: Department of Oncology, Tianyou Hospital Affiliated to Tongji University, Shanghai 200331, PR China.
authors: Shiyu
authors: S
authors: Chen
authors: Department of Oncology, Tianyou Hospital Affiliated to Tongji University, Shanghai 200331, PR China.
authors: Bing
authors: B
authors: Dan
authors: Department of Oncology, Tianyou Hospital Affiliated to Tongji University, Shanghai 200331, PR China.
authors: Cuihua
authors: C
authors: Wang
authors: Department of Oncology, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, PR China. Electronic address: shtumor@163.com.
authors: Yajie
authors: Y
authors: Wang
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D019295:Computational Biology; D030541:Databases, Genetic; D005260:Female; D006597:Fructose-Bisphosphatase / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis; D006801:Humans; D053208:Kaplan-Meier Estimate; D061986:MCF-7 Cells; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D060449:Wnt Signaling Pathway
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D006597:Fructose-Bisphosphatase; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
keywords: -Catenin pathway; Breast cancer; FBP1; GSEA; Oncomine; Wnt/βbeta