American Association for Cancer Research
15357163mct210509-sup-267140_3_supp_7435365_r09jg1.xlsx (25.77 kB)

Table S3 from Anastrozole Regulates Fatty Acid Synthase in Breast Cancer

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posted on 2023-04-03, 18:48 authored by Junmei Cairns, James N. Ingle, Krishna R. Kalari, Matthew P. Goetz, Richard M. Weinshilboum, Huanyao Gao, Hu Li, Mehrab Ghanat Bari, Liewei Wang

Table S3 shows Overlapped genes (highlighted) between ERα CHIPseq in the presence of anastrozole and RNAseq in the presence of anastrozole.


Breast Cancer Research Foundation (BCRF)




Our previous matched case–control study of postmenopausal women with resected early-stage breast cancer revealed that only anastrozole, but not exemestane or letrozole, showed a significant association between the 6-month estrogen concentrations and risk of breast cancer. Anastrozole, but not exemestane or letrozole, is a ligand for estrogen receptor α. The mechanisms of endocrine resistance are heterogenous and with the new mechanism of anastrozole, we have found that treatment of anastrozole maintains fatty acid synthase (FASN) protein level by limiting the ubiquitin-mediated FASN degradation, leading to increased breast cancer cell growth. Mechanistically, anastrozole decreases the guided entry of tail-anchored proteins factor 4 (GET4) expression, resulting in decreased BCL2-associated athanogene cochaperone 6 (BAG6) complex activity, which in turn, prevents RNF126-mediated degradation of FASN. Increased FASN protein level can induce a negative feedback loop mediated by the MAPK pathway. High levels of FASN are associated with poor outcome only in patients with anastrozole-treated breast cancer, but not in patients treated with exemestane or letrozole. Repressing FASN causes regression of breast cancer cell growth. The anastrozole-FASN signaling pathway is eminently targetable in endocrine-resistant breast cancer.