Role of estrogen receptor coregulators in endocrine resistant breast cancer

Altwegg, Kristin A.; Vadlamudi, Ratna K.

doi:10.37349/etat.2021.00052

Cited by 11 publications

(8 citation statements)

References 131 publications

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“…Finally, the carboxyl terminus, which is known as the ligand-binding domain (LBD), contains the binding sites for co-activators, co-repressors, and the estrogen binding region [ 15 ]. LBD also includes a ligand-dependent activation domain (AF2) [ 16 ].…”

Section: The Structure Of Estrogen Receptorsβ (Erβ)mentioning

confidence: 99%

Signal Crosstalk and the Role of Estrogen Receptor beta (ERβ) in Prostate Cancer

Liu

Jiang

2022

Med Sci Monit

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Prostate cancer remains the most prevalent cancer among men worldwide; however, as a sex hormone-dependent cancer, sex hormones and their receptor signaling play an important role in the development and progression of cancer. Most current treatment options for prostate cancer thus revolve around the inhibition of androgen signaling (eg, ADT), which, although effective in the early stages, eventually progresses to treatment-resistant prostate cancer with no effective follow-up options. Recent studies have shown that among the nuclear receptor family members, in addition to androgen receptors, estrogen receptor (ER) plays an important biological function as a transcription factor and regulatory protein in various cancers, acting either directly or indirectly by forming homodimers or heterodimers with ligands. In this paper, we review the application of ERβ in animal models and in vitro experiments in the last 5 years, as well as the presence and role of some of its splice variants. We summarize the overview and update of ERβ in prostate cancer, and provide a corresponding analysis of some current research disagreements. Its crosstalk action on some important cancer growth-related signaling pathways (eg, TGF-β and ERK), regulation of downstream target proteins (eg, nuclear translocation of EGFR and expression of oncogenic-related protein MMP-2), and interactions with related ERβ co-regulators (eg, ZFHX3), agonists, and antagonists in prostate cancer are highlighted, and the resulting effects on tumor progression are described. In addition, the paper describes its current potential clinical application as a novel therapeutic strategy and some of the challenges it faces.

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Section: The Structure Of Estrogen Receptorsβ (Erβ)mentioning

confidence: 99%

Signal Crosstalk and the Role of Estrogen Receptor beta (ERβ) in Prostate Cancer

Liu

Jiang

2022

Med Sci Monit

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“…6 Estrogens binding to the ER can promote cell division and increase the risk of replication errors, resulting in cancer development and progression. 7 ER-positive breast cancers are treated via endocrine therapy. 8 Despite tremendous progress of endocrine treatments in the early stage of ER-positive breast cancer, still about 20% of patients will suffer a metastasis in <10 years.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic significance of long noncoding RNAs in estrogen receptor‐positive breast cancer

Alzahrani,

Saleh,

latypova

et al. 2024

Cell Biochemistry & Function

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About 70% of cases of breast cancer are compromised by Estrogen‐positive breast cancer. Through its regulation of several processes, including cell proliferation, cell cycle progression, and apoptosis, Estrogen signaling plays a pivotal role in the genesis and progression of this particular kind of breast cancer. One of the best treatment strategies for treating Estrogen‐positive breast cancer is blocking Estrogen signaling. However, patients' treatment failure is mainly caused by the emergence of resistance and metastases, necessitating the development of novel therapeutic targets. Numerous studies have shown long noncoding RNAs (lncRNAs) to play a role in Estrogen‐mediated carcinogenesis. These lncRNAs interact with co‐regulators and the Estrogen signaling cascade components, primarily due to Estrogen activation. Vimentin and E‐cadherin are examples of epithelial‐to‐mesenchymal transition markers, and they regulate genes involved in cell cycle progression, such as Cyclins, to affect the growth, proliferation, and metastasis of Estrogen‐positive breast cancer. Furthermore, a few of these lncRNAs contribute to developing resistance to chemotherapy, making them more desirable targets for enhancing results. Thus, to shed light on the creation of fresh approaches for treating this cancer, this review attempts to compile recently conducted studies on the relationship between lncRNAs and the advancement of Estrogen‐positive breast cancer.

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“…Endocrine resistance can emerge from different key mechanisms [ 9 , 10 ]. It can result from impaired estrogen signaling resulting from downregulation, mutation, aberrant phosphorylation, or altered stability of ERα, from an imbalance between ER coactivator and corepressor proteins or ER-binding transcription factors, and from ligand-independent activation of estrogen receptors [ 11 , 12 , 13 , 14 ]. Other mechanisms of endocrine resistance include MYC overexpression, amplification of cyclin D1 ( CCND1 ) or MDM2 gene, reduced activity of CYP2D6, the enzyme responsible for activation of tamoxifen, aberrant promoter methylation which, e.g., leads to activation of the Akt/mTOR pathway, and activation of other estrogen-independent growth-promoting pathways triggered by mechanisms such as ERBB2 amplification, bypassing the action of endocrine therapies [ 8 , 9 , 15 , 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Non-Coding RNAs Modulating Estrogen Signaling and Response to Endocrine Therapy in Breast Cancer

Treeck¹,

Ortmann²

2023

Cancers

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The largest part of human DNA is transcribed into RNA that does not code for proteins. These non-coding RNAs (ncRNAs) are key regulators of protein-coding gene expression and have been shown to play important roles in health, disease and therapy response. Today, endocrine therapy of ERα-positive breast cancer (BC) is a successful treatment approach, but resistance to this therapy is a major clinical problem. Therefore, a deeper understanding of resistance mechanisms is important to overcome this resistance. An increasing amount of evidence demonstrate that ncRNAs affect the response to endocrine therapy. Thus, ncRNAs are considered versatile biomarkers to predict or monitor therapy response. In this review article, we intend to give a summary and update on the effects of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) on estrogen signaling in BC cells, this pathway being the target of endocrine therapy, and their role in therapy resistance. For this purpose, we reviewed articles on these topics listed in the PubMed database. Finally, we provide an assessment regarding the clinical use of these ncRNA types, particularly their circulating forms, as predictive BC biomarkers and their potential role as therapy targets to overcome endocrine resistance.

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Role of estrogen receptor coregulators in endocrine resistant breast cancer

Cited by 11 publications

References 131 publications

Signal Crosstalk and the Role of Estrogen Receptor beta (ERβ) in Prostate Cancer

Signal Crosstalk and the Role of Estrogen Receptor beta (ERβ) in Prostate Cancer

Therapeutic significance of long noncoding RNAs in estrogen receptor‐positive breast cancer

Non-Coding RNAs Modulating Estrogen Signaling and Response to Endocrine Therapy in Breast Cancer

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