FGFR1 underlies obesity-associated progression of estrogen receptor-positive breast cancer after estrogen deprivation.

ABSTRACT: Obesity increases breast cancer mortality by promoting resistance to therapy. Here, we identified regulatory pathways in estrogen receptor-positive (ER-positive) tumors that were shared between patients with obesity and those with resistance to neoadjuvant aromatase inhibition. Among these was fibroblast growth factor receptor 1 (FGFR1), a known mediator of endocrine therapy resistance. In a preclinical model with patient-derived ER-positive tumors, diet-induced obesity promoted a similar gene expression signature and sustained the growth of FGFR1-overexpressing tumors after estrogen deprivation. Tumor FGFR1 phosphorylation was elevated with obesity and predicted a shorter disease-free and disease-specific survival for patients treated with tamoxifen. In both human and mouse mammary adipos

SUBMITTER: Wellberg EA 

PROVIDER: S-EPMC6124402 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature