Estrogen Receptor Signaling in Cancer

Langdon, Simon P.

doi:10.3390/cancers12102744

Cited by 13 publications

(10 citation statements)

References 7 publications

(17 reference statements)

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“…Furthermore, we found 17 downregulated candidates that were also contributing to the estrogen signature found in by GSEA, i.e., ELF3 , SERPINA3 , SGK1 , SCNN1A , DLC1 , KRT15 , KRT19, or THSD4 . Estrogen signaling play a major role favoring proliferation in some cancers [ 76 ]. The inhibition of this signaling pathway by MS275+Gem could be responsible for the antiproliferative effect observed on MIA PaCa-2 cells.…”

Section: Resultsmentioning

confidence: 99%

Synergistic Antitumoral Effect of Epigenetic Inhibitors and Gemcitabine in Pancreatic Cancer Cells

et al. 2022

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Epigenetic modifications could drive some of the molecular events implicated in proliferation, drug resistance and metastasis of pancreatic ductal adenocarcinoma (PDAC). Thus, epigenetic enzyme inhibitors could be the key to revert those events and transform PDAC into a drug-sensitive tumor. We performed a systematic study with five different epigenetic enzyme inhibitors (1, UVI5008, MS275, psammaplin A, and BIX01294) targeting either Histone Deacetylase (HDAC) 1 or 1/4, DNA methyltransferase 3a (DNMT3a), Euchromatic histone lysine methyltransferase 2 (EHMT2), or Sirtuin 1 (SIRT1), as well as one drug that restores the p53 function (P53R3), in three different human PDAC cell lines (SKPC-1, MIA PaCa-2, and BxPC-3) using 2D and 3D cell cultures. The synergistic effect of these antitumoral drugs with gemcitabine was tested and the most efficient combinations were characterized by RNA-seq. The inhibition of HDAC1/4 (MS275), HDAC1/4/SIRT1/DNMT3a (UVI5008) or EHMT2 (BIX01294) induced a significant reduction on the cell viability, even in gemcitabine-resistance cells. The combination of UVI5008 or MS275 with gemcitabine induced a synergistic effect at low concentration and the RNA-Seq analysis revealed some synergy candidate genes as potential biomarkers. Reverting aberrant epigenetic modifications in combination with gemcitabine offers an alternative treatment for PDAC patients, with an important reduction of the therapeutic dose.

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Section: Resultsmentioning

confidence: 99%

Synergistic Antitumoral Effect of Epigenetic Inhibitors and Gemcitabine in Pancreatic Cancer Cells

et al. 2022

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“…The zeste homolog (EZH) 2-mediates epigenetic silencing of ERα cofactor growth regulation by estrogen in BC 1 (GREB1) contributes to the development of tamoxifen resistance [100]. As an adaptive response to endocrine therapy, tumors acquire mutations in the ERα-LBD [30,101,102]. These mtERα proteins have high constitutive transcriptional activity even in the absence of E2 [30,71].…”

Section: Coregulators and Endocrine Therapy Resistancementioning

confidence: 99%

Role of estrogen receptor coregulators in endocrine resistant breast cancer

Altwegg

Vadlamudi

2021

Exploration of Targeted Anti-Tumor Therapy

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Breast cancer (BC) is the most ubiquitous cancer in women. Approximately 70-80% of BC diagnoses are positive for estrogen receptor (ER) alpha (ERα). The steroid hormone estrogen [17β-estradiol (E2)] plays a vital role both in the initiation and progression of BC. The E2-ERα mediated actions involve genomic signaling and non-genomic signaling. The specificity and magnitude of ERα signaling are mediated by interactions between ERα and several coregulator proteins called coactivators or corepressors. Alterations in the levels of coregulators are common during BC progression and they enhance ligand-dependent and ligand-independent ERα signaling which drives BC growth, progression, and endocrine therapy resistance. Many ERα coregulator proteins function as scaffolding proteins and some have intrinsic or associated enzymatic activities, thus the targeting of coregulators for blocking BC progression is a challenging task. Emerging data from in vitro and in vivo studies suggest that targeting coregulators to inhibit BC progression to therapy resistance is feasible. This review explores the current state of ERα coregulator signaling and the utility of targeting the ERα coregulator axis in treating advanced BC.

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“…Contradict to this scenario, in a study on the effects of ER status and other prognostic factors, including BRCA2 mutation analysis, positive ER status was associated with a higher risk of death than negative ER status on further confirming that ER status is an adverse prognostic factor [ 22 ]. Furthermore, the mutation in ER gene ESR1 has recently been recognized with resistance to estrogen deprivation and relative resistance to tamoxifen and fulvestrant [ 23 , 24 ]. Therefore targeting ERα for degradation is an effective treatment in too severe metastatic ER-positive BC stages.…”

Section: Er Dependence On Bcmentioning

confidence: 99%

Emerging role of pioneer transcription factors in targeted ERα positive breast cancer

Pavithran

Kumavath

2021

Exploration of Targeted Anti-Tumor Therapy

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Transcription factors (TFs) are modular protein groups that preferably bind to DNA sequences and guide genomic expression through transcription. Among these key regulators, “pioneer factors” are an emerging class of TFs that specifically interact with nucleosomal DNA and facilitate accessible genomic binding sites for the additional TFs. There is growing evidence of these specialized modulators in particular malignancies, as highlighted by agents’ clinical efficacy, specifically targeting nuclear hormone receptors. They have been implicated in multiple cancers more recently, with a high proportion inculpating on hormone influential cancers. Moreover, extended crosstalk and cooperation between ERα pioneering factors in estrogen-dependent breast cancer (BC) remain elucidated. This review discusses on the recent advances in our understanding of pioneer TFs in cancer, especially highlighting its potentiality to modulate chromatin condensation to permit ERα recruitment in BC cells. Through the study it was concluded that the highly prospected pioneer TFs in BC, including FOXA1, TLE1, PBX1, and GATA3, possess the potential therapeutic significance and further innovations in the field could yield targeted therapy in cancer treatment.

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Estrogen Receptor Signaling in Cancer

Abstract: Estrogen receptor signaling plays

Cited by 13 publications

References 7 publications

Synergistic Antitumoral Effect of Epigenetic Inhibitors and Gemcitabine in Pancreatic Cancer Cells

Synergistic Antitumoral Effect of Epigenetic Inhibitors and Gemcitabine in Pancreatic Cancer Cells

Role of estrogen receptor coregulators in endocrine resistant breast cancer

Emerging role of pioneer transcription factors in targeted ERα positive breast cancer

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