Figure 9

Possible mechanisms of inhibition of mammary tumorigenesis by fibroblast growth factor receptor (FGFR)4 deficiency. Deficiency of hepatic metabolic regulator FGFR4 has little effect on breast cellularity and function where FGFR4 is not at play. The deficiency causes systemic metabolic changes and constitutive elevation of expression of systemic FGF21 which is normally elevated only during diverse hepatic stress conditions that are disease-suppressive. FGF21 specifically acts on adipocytes both in fat depots and breast. Both circulating and breast microenvironmental secretory products from adipocytes affect cellular and metabolic behavior of breast epithelial cells. Systemic changes in metabolism governed by hepatocyte FGFR4-betaKlotho (KLB) and both systemic and microenvironmental changes governed by adipocyte FGFR1-KLB impact breast parenchymal cell behavior and tumor progression. A + M: adipokines and metabolic effects.