Estrogen Receptor Signaling in Radiotherapy: From Molecular Mechanisms to Clinical Studies

Chen, Rong; Meinert, Étienne Fasolt Richard Corvin; Heß, Jochen

doi:10.3390/ijms19030713

Cited by 23 publications

(14 citation statements)

References 98 publications

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“…OAC tissues [ 93 , 94 ] as well as OAC cell lines have been found to express ERα and ERβ [ 28 ] and OAC cell lines respond to treatment with ER antagonists [ 27 , 95 ]. ER signaling also contributes to radioresistance [ 96 ]. Furthermore, ERα and ERβ, have also been reported to interact with multiple signaling pathways such as MAPK, WNT/β-catenin, EGFR, and p53 [ 97 ].…”

Section: Discussionmentioning

confidence: 99%

Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression

Eichelmann

Mayne

Chiam

et al. 2021

IJMS

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TP53 gene mutations occur in 70% of esophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the predicted mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53.

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Section: Discussionmentioning

confidence: 99%

Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression

Eichelmann

Mayne

Chiam

et al. 2021

IJMS

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“…RT-induced overexpression of hormonal receptors, including AR and ER, plays a vital role in mediating radioresistance in prostate and breast cancers, respectively ( 113 , 114 ). In castration-resistant prostate cancer (CRPC) cells, the PROTAC ARD-61 can efficiently degrade AR and inhibited cancer cell proliferation with half-maximum inhibitory concentration (IC:50) values <500 nM, regardless of AR mutations, and expression status of AR splice variants, such as AR splice variant-7 (AR-V7) ( 102 ).…”

Section: Proteolysis Targeting Chimeras (Protacs)mentioning

confidence: 99%

Targeting Cullin-RING E3 Ligases for Radiosensitization: From NEDDylation Inhibition to PROTACs

Zheng

Tao

2020

Front. Oncol.

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As a dynamic regulator for short-lived protein degradation and turnover, the ubiquitin-proteasome system (UPS) plays important roles in various biological processes, including response to cellular stress, regulation of cell cycle progression, and carcinogenesis. Over the past decade, research on targeting the cullin-RING (really interesting new gene) E3 ligases (CRLs) in the UPS has gained great momentum with the entry of late-phase clinical trials of its novel inhibitors MLN4924 (pevonedistat) and TAS4464. Several preclinical studies have demonstrated the efficacy of MLN4924 as a radiosensitizer, mainly due to its unique cytotoxic properties, including induction of DNA damage response, cell cycle checkpoints dysregulation, and inhibition of NF-κB and mTOR pathways. Recently, the PROteolysis TArgeting Chimeras (PROTACs) technology was developed to recruit the target proteins for CRL-mediated polyubiquitination, overcoming the resistance that develops inevitably with traditional targeted therapies. First-in-class cell-permeable PROTACs against critical radioresistance conferring proteins, including the epidermal growth factor receptor (EGFR), androgen receptor (AR) and estrogen receptor (ER), cyclin-dependent kinases (CDKs), MAP kinase kinase 1 (MEK1), and MEK2, have emerged in the past 5 years. In this review article, we will summarize the most important research findings of targeting CRLs for radiosensitization.

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“…In 2014, the incidence rate of breast cancer in China was 18.65%, and it is growing at a rate of 3% per year ( 2 ), which has become one of the main threats to the health of women; it is a great burden on society and requires further research. There are numerous treatments for breast cancer, including targeted molecular therapy, chemotherapy, radiotherapy and surgery ( 3 ). Although considerable progress has been achieved in the medical treatment of breast cancer, there is no radically effective treatment for patients with breast cancer, and the prognosis of clinical treatment remains extremely poor.…”

Section: Introductionmentioning

confidence: 99%

Regulatory effect of microRNA‑223‑3p on breast cancer cell processes via the Hippo/Yap signaling pathway

Wang

et al. 2021

Oncol Lett

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According to the 2018 global cancer statistics, the incidence and mortality rates of breast cancer are increasing gradually, which seriously threatens the health of women. MicroRNA-223-3p (miR-223-3p) can promote the proliferation and invasion of breast cancer cells. Hippo/Yes-related protein (Yap) signaling pathway activation has been found in a variety of tumors. The present study aimed to investigate the potential mechanism of miR-223-3p in breast cancer. The Cell Counting Kit-8 assay was used to detect cell viability and flow cytometry was used to detect apoptosis. The abilities of cell migration and invasion were detected using scratch and Transwell assays, as well as reverse transcription-quantitative PCR and western blotting to detect gene and protein expression, respectively. The current results demonstrated that miR-223-3p transcription levels were increased in breast cancer cells, and inhibition of miR-223-3p gene expression decreased cell proliferation, migration and invasion. Additionally, inhibition of miR-223-3p expression inhibited epithelial-mesenchymal transition (EMT) in breast cancer cells. miR-223-3p promoted cell proliferation, migration, invasion and EMT, and the western blotting results demonstrated that miR-223-3p inhibition increased the phosphorylation of Yap1 and the protein expression levels of large tumor suppressor kinase 1. In conclusion, results from the present results suggested that miR-223-3p may promote cell proliferation, migration, invasion and EMT through the Hippo/Yap signaling pathway. Therefore, miR-223-3p may be a potential biomarker for breast cancer.

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Estrogen Receptor Signaling in Radiotherapy: From Molecular Mechanisms to Clinical Studies

Cited by 23 publications

References 98 publications

Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression

Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression

Targeting Cullin-RING E3 Ligases for Radiosensitization: From NEDDylation Inhibition to PROTACs

Regulatory effect of microRNA‑223‑3p on breast cancer cell processes via the Hippo/Yap signaling pathway

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