2021
DOI: 10.3390/cells10071633
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NR4A1 Regulates Tamoxifen Resistance by Suppressing ERK Signaling in ER-Positive Breast Cancer

Abstract: Endocrine therapy is used to treat estrogen receptor (ER)-positive breast cancer. Tamoxifen is effective against this cancer subtype. Nonetheless, approximately 30% of patients treated with tamoxifen acquire resistance, resulting in therapeutic challenges. NR4A1 plays key roles in processes associated with carcinogenesis, apoptosis, DNA repair, proliferation, and inflammation. However, the role of NR4A1 in tamoxifen-resistant ER-positive breast cancer has not yet been elucidated. Here, we propose that NR4A1 is… Show more

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Cited by 14 publications
(17 citation statements)
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“…Te signifcant gene sets conformed to the standards of "nominal (NOM) p value <0.05" and "false discovery rate (FDR) q-value <0. 25. "…”
Section: Gene Set Enrichment Analysis (Gsea) and Analysis Ofmentioning
confidence: 99%
“…Te signifcant gene sets conformed to the standards of "nominal (NOM) p value <0.05" and "false discovery rate (FDR) q-value <0. 25. "…”
Section: Gene Set Enrichment Analysis (Gsea) and Analysis Ofmentioning
confidence: 99%
“…Other molecules have been implicated in endocrine resistance with mechanisms involving ERK activation, including NR4A1 (Nuclear Receptor Subfamily 4 Group A Member 1) [ 117 ], Krüppel-like factor 4 (KLF4) [ 118 ], the nuclear receptor coregulator PELP1 [ 119 ], placenta specific 8 (PLAC8) [ 120 ], fatty acid synthase (FASN) [ 121 ], and the ubiquitin ligase TRIM RING finger protein TRIM2 [ 122 ].…”
Section: Ras/raf/mek/erk Pathway In Luminal Cancers and Resistance To...mentioning
confidence: 99%
“…In addition, ERα can be activated in an estrogen- independent manner by a large panel of factors, including epidermal growth factor (EGF) (Ignar-Trowbridge et al , 1992; Ignar-Trowbridge et al , 1993), insulin and insulin-like growth factors (IGF) (Newton et al , 1994), PI3K (Campbell et al , 2001), Akt (Campbell et al , 2001; Martin et al , 2000), and hypoxia-inducible factor 1 α (HIF1α) (Cho et al , 2006; Bennesch & Picard, 2015) (see detailed list at https://www.picard.ch/downloads/Factors.pdf). Through various domains, ERα can interact with a plethora of proteins that regulate its activity, such as the MAPKs ERK1/ERK2 (ERK1/2) (Chen et al , 2002; Kato et al , 1995; Kim et al , 2021; Vafeiadou et al , 2022; Li et al , 2012; Mueller et al , 2000; Bunone et al , 1996), mTOR (Alayev et al , 2016), cyclin-dependent kinase inhibitor 1 (p21) (Fritah et al , 2005; Redeuilh et al , 2002; Abukhdeir et al , 2008), and poly (ADP-ribose) polymerase 1 (PARP1) (Schiewer & Knudsen, 2014; Zhang et al , 2013; Pulliam et al , 2019; Gadad et al , 2021) (see the updated list of ERα interactors at https://www.picard.ch/downloads).…”
Section: Introductionmentioning
confidence: 99%
“…Resistance to tamoxifen can be attributed to multiple mechanisms, including loss of ERα expression or function due to genetic mutations, alterations in the levels of co-regulatory factors (Osborne et al , 2003), upregulation of oncogenic signal transduction pathways, and ligand-independent activation of ERα (Kato et al , 1995; Shim et al , 2000; Coutts & Murphy, 1998; Gee et al , 2001; Clark et al , 2002; Gutierrez et al , 2005; Bennesch & Picard, 2015). For example, ERK1/2 play a critical role in breast cancer and their hyperactivation is associated with tamoxifen resistance and poor prognosis (Gee et al , 2001; Coutts & Murphy, 1998; Shim et al , 2000; Chen et al , 2002; Kato et al , 1995; Kim et al , 2021; Vafeiadou et al , 2022; Li et al , 2012; Mueller et al , 2000; Bunone et al , 1996). ERK1/2 can stimulate cell growth independently of ERα or through signaling crosstalk with ERα.…”
Section: Introductionmentioning
confidence: 99%
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