NDLI: Deficiency of metabolic regulator FGFR4 delays breast cancer progression through systemic and microenvironmental metabolic alterations

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Acidosis induces reprogramming of cellular metabolism to mitigate oxidative stress

PGC-1α supports glutamine metabolism in breast cancer

Deficiency of metabolic regulator FGFR4 delays breast cancer progression through systemic and microenvironmental metabolic alterations

The metabolic demands of cancer cells are coupled to their size and protein synthesis rates

Quinoline 3-sulfonamides inhibit lactate dehydrogenase A and reverse aerobic glycolysis in cancer cells

LKB1 is a central regulator of tumor initiation and pro-growth metabolism in ErbB2-mediated breast cancer

Ets-1 global gene expression profile reveals associations with metabolism and oxidative stress in ovarian and breast cancers

Linking vitamin B1 with cancer cell metabolism

Cerebellar granule neuron progenitors are the source of Hk2 in the postnatal cerebellum

The role of Bergmann glial cells in cerebellar development

Expression and phosphorylation of the AS160_v2 splice variant supports GLUT4 activation and the Warburg effect in multiple myeloma

Reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells

Respiratory complex I is essential to induce a Warburg profile in mitochondria-defective tumor cells

Calorie restriction and cancer prevention: a mechanistic perspective

Balancing glycolytic flux: the role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatases in cancer metabolism

Metabolic changes in cancer cells upon suppression of MYC

p53 promotes the expression of gluconeogenesis-related genes and enhances hepatic glucose production

Activated lymphocytes as a metabolic model for carcinogenesis

Hexokinase-2-mediated aerobic glycolysis is integral to cerebellar neurogenesis and pathogenesis of medulloblastoma

Monitoring metabolic responses to chemotherapy in single cells and tumors using nanostructure-initiator mass spectrometry (NIMS) imaging

Sterol regulatory element binding protein-dependent regulation of lipid synthesis supports cell survival and tumor growth

The long and winding road to the mitochondrial pyruvate carrier

Why Cancer & Metabolism? Why now?

Deficiency of metabolic regulator FGFR4 delays breast cancer progression through systemic and microenvironmental metabolic alterations

Content Provider	Springer Nature : BioMed Central
Author	Luo, Yongde Yang, Chaofeng Ye, Min Jin, Chengliu Abbruzzese, James L Lee, Mong-Hong Yeung, Sai-Ching J McKeehan, Wallace L
Abstract	Background Endocrine FGF21 and FGF19 target adipocytes and hepatocytes through betaKlotho (KLB) and FGFR tyrosine kinases effecting glucose, lipid and energy metabolism. Both factors alleviate obesity and metabolic abnormalities which are contributing factors to breast tumor progression. Genomic manipulation of hepatic FGFR4 has uncovered roles of endocrine FGF signaling in both metabolic and cellular homeostasis. Here we determined whether systemic and microenvironmental metabolic alterations caused by the FGFR4 deficiency affect tumorigenesis in breast where FGFR4 is negligible. Breast tumors were induced in the bigenic mice with ablation of FGFR4 and overexpression of TGFα that activates Her2 in the ductal and lobular epithelium surrounded by adipocytes. Mammary tumorigenesis and alterations in systemic and breast microenvironmental metabolic parameters and regulatory pathways were analyzed. Results Ablation of FGFR4 had no effect on cellular homeostasis and Her2 activity of normal breast tissue. However, the absence of FGFR4 reduced TGFα–driven breast tumor incidence and progression and improved host survival. Notable increases in hepatic and serum FGF21, ileal FGF15/19, adiponectin and adipsin, and decreases in systemic Fetuin A, IGF-1, IGFBP-1, RBP4 and TIMP1 were observed. The ablation affected adipogenesis and secretory function of adipocytes as well as lipogenesis, glycolysis and energy homeostasis associated with the functions of mitochondria, ER and peroxisomes in the breast and tumor foci. Treatment with a chemical inhibitor of NAMPT involved in the pathways inhibited the growth and survival of breast tumor cells and tumor-initiating cell-containing spheres. The FGFR4 ablation also caused elevation of inflammatory factors in the breast. Conclusions Although the primary role of FGFR4 in metabolism occurs in hepatocytes, its ablation results in a net inhibitory effect on mammary tumor progression. We suggest that the tumor-delaying effect of FGFR4 deficiency may be in large part due to elevated anti-obesogenic FGF21 that triggers tumor-suppressing signals from both peripheral and breast adipocytes. The predominant changes in metabolic pathways suggested roles of metabolic effects from both peripheral and breast adipocytes on metabolic reprogramming in breast epithelial cells that contribute to the suppression of tumor progression. These results provide new insights into the contribution of systemic and microenvironmental metabolic effects controlled by endocrine FGF signaling to breast carcinogenesis.
Related Links	https://cancerandmetabolism.biomedcentral.com/counter/pdf/10.1186/2049-3002-1-21.pdf
Ending Page	20
Page Count	20
Starting Page	1
File Format	HTM / HTML
ISSN	20493002
DOI	10.1186/2049-3002-1-21
Journal	Cancer & Metabolism
Issue Number	1
Volume Number	1
Language	English
Publisher	BioMed Central
Publisher Date	2013-11-25
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Metabolomics Metabolic Diseases Imaging Radiology Cell Biology Adipokines Breast cancer endocrine fibroblast growth factor (eFGF) Fibroblast growth factor receptor (FGFR) Inflammatory response Metabolism Microenvironmental and systemic effects Transforming growth factor alpha (TGFα)
Content Type	Text
Resource Type	Article
Subject	Cancer Research
Journal Impact Factor	6/2023
5-Year Journal Impact Factor	5.4/2023

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Deficiency of metabolic regulator FGFR4 delays breast cancer progression through systemic and microenvironmental metabolic alterations

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Deficiency of metabolic regulator FGFR4 delays breast cancer progression through systemic and microenvironmental metabolic alterations