Year: 2025
Type: preprint
Abstract: Obesity is predicted to become the largest modifiable risk factor for breast cancer in postmenopausal women, yet the mechanisms underlying this association are unclear. We identified a novel role for the endogenous oxylipin 9S-HODE, secreted by lean adipocytes, to induce ferroptosis in breast cancer cells while sparing normal breast epithelial cells. Obese adipocytes fail to secrete 9S-HODE, suggesting that the loss of ferroptosis induction significantly contributes to the acceleration of obesity-associated breast cancer. Consequently, the inhibition of ferroptosis accelerates breast cancer in lean, but not obese, mice. Further, 9S-HODE inhibits the growth of patient-derived breast cancer organoids, and supplementing 9S-HODE into tumors in obese mice is sufficient to reduce tumor burden, underscoring its potential as a therapeutic agent.
Authors: Meghan C. Curtin, Abigail E. Jackson, Elisabeth A. Brown, J. Alan Maschek, David Lum, James E. Cox, Alana L. Welm, Keren I. Hilgendorf
Institutions: University of Utah, Huntsman Cancer Institute
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G2151844907, G2552051766, BREAKING BARRIERS IN DRUG DEVELOPMENT FOR BREAST CANCER THERAPEUTIC STUDIES ON PATIENT TUMORS IN IMMUNE-COMPETENT MICE WITH HUMAN STEM CELL, G4204565932, Agilent 6550 QTOF system for U of Utah, G4563853763, G5145111290, G534868654, Agilent 7200 GC/Q-TOF for the University of Utah, G7146483737, G7941272330, G858682239, Q-ToF Mass Spectrometer for the University of Utah MS and Proteomics Core, G9000028008, G9000153296, Huntsman Cancer Institute (HCI) Cancer Genetics, Epigenetics, Models, and Signaling (Cancer GEMS) Training Program, Ciliary signaling mechanisms regulating white adipose tissue expansion, G901144248
OpenAlex ID: W4412550418