AUTHOR=Yan Chaojun , Gao Ronghui , Gao Chuan , Hong Kai , Cheng Meng , Liu Xiaojing , Zhang Qing , Zhang Jing 

TITLE=FDXR drives primary and endocrine-resistant tumor cell growth in ER+ breast cancer via CPT1A-mediated fatty acid oxidation

JOURNAL=Frontiers in Oncology

VOLUME=Volume 13 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1105117

DOI=10.3389/fonc.2023.1105117

ISSN=2234-943X

ABSTRACT=The majority of breast cancers (BCs) expressing estrogen receptor (ER) have shown endocrine resistance. Our previous study demonstrated that ferredoxin reductase (FDXR) promoted mitochondrial function and ER+ breast tumorigenesis. Here, integrative analyses with targeted metabolomics assays and gene expression profiling showed that FDXR potentiated fatty acid oxidation (FAO) through positive regulation of carnitine palmitoyltransferase 1A (CPT1A) expression. Treatment with an ER antagonist (tamoxifen) or degrader (fulvestrant) increased the expression of FDXR and CPT1A. In line with this finding, we found that the FDXR-CPT1A-FAO axis was required for primary and endocrine-resistant breast cancer cell growth. Therapeutically, combining endocrine therapy with FAO inhibitors synergistically reduced primary and endocrine-resistant breast cancer cell growth, thus providing a potential combinatory treatment for ER+ breast cancer.