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HOXA5 confers tamoxifen resistance via the PI3K/AKT signaling pathway in ER-positive breast cancer

Authors
 Clara Yuri Kim  ;  Yu Cheon Kim  ;  Ji Hoon Oh  ;  Myoung Hee Kim 
Citation
 JOURNAL OF CANCER, Vol.12(15) : 4626-4637, 2021-06 
Journal Title
JOURNAL OF CANCER
Issue Date
2021-06
Keywords
AKT ; HOXA5 ; breast cancer ; p53 ; tamoxifen resistance
Abstract
Tamoxifen is a commonly used drug to treat estrogen receptor-positive patients with breast cancer. Despite the outstanding efficacy of tamoxifen, approximately one-third of patients develop resistance toward it, thereby presenting a therapeutic challenge. HOX genes may be involved in the acquisition of tamoxifen resistance. In this study, we identified HOXA5, a member of the HOX gene family, as a marker of tamoxifen resistance. Using ChIP assay, we found that HOXA5 expression was significantly overexpressed in tamoxifen-resistant MCF7 (TAMR) breast cancer cells because of reduced H3K27me3 binding. HOXA5 upregulation resulted in activation of the PI3K/AKT signaling cascade, which in turn, led to p53 and p21 reduction, ultimately making the TAMR cells less apoptotic. Furthermore, elevated HOXA5 expression resulted in breast cancer cells acquiring more mesenchymal-like and stem cell traits associated with aggressive breast cancer phenotypes. In conclusion, our results delineate a mechanism by which HOXA5 promotes tumorigenesis, cancer progression, and tamoxifen resistance in breast cancer cells.
Files in This Item:
T202102624.pdf Download
DOI
10.7150/jca.59740
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Hee(김명희) ORCID logo https://orcid.org/0000-0001-5652-1452
Kim, Clara Yuri(김유리)
Oh, Ji Hoon(오지훈) ORCID logo https://orcid.org/0000-0001-6619-5515
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184208
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