Enzalutamide resistance in prostate cancer cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA633640 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11809312.fastq.gz | Fastqsanger.gz | |||
| SRR11809313.fastq.gz | Fastqsanger.gz | |||
| SRR11809314.fastq.gz | Fastqsanger.gz | |||
| SRR11809315.fastq.gz | Fastqsanger.gz | |||
| SRR11809316.fastq.gz | Fastqsanger.gz |
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Project description:Enzalutamide resistance in C42-B prostate cancer cells
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Project description:Castration resistant prostate cancer (CRPC) develops resistance to antiandrogens affecting Androgen Receptor (AR) signaling through a variety of mechanism. Because of this, the efficacy of androgen receptor targeted therapy remains limited for many patients with CRPC. We developed LNCaP-enzalutamide (ENZU) and resistance cells to study changes in transcriptomic profile compared to parental cells.
2020-12-31 | GSE150807 | GEO
Project description:To investigate the mechanisms of drug resistance and castration resistance in prostate cancer, we performed proteomic sequencing on androgen-dependent prostate cancer cells (LNCaP) and androgen-independent cells (AI) treated with enzalutamide.
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Project description:Enzalutamide, a second-generation androgen receptor (AR) antagonist, has represented the association with improved overall survival in men with prostate cancer (PCa). However, PCa patients receiving enzalutamide will eventually develop resistance through various mechanisms without effective regimens. Here, we observed a higher level of formin-like 2 (FMNL2) in enzalutamide-resistant PCa cells. Functionally, FMNL2 knockdown partially re-sensitized enzalutamide-resistant PCa cells. Mechanistically, FMNL2 directly interacted with SRC kinase through FMNL2-FH1 and SRC-SH3 domain, which induced AR translocation from the cytoplasm to the nucleus, resulting in increased expression of the AR-targeted genes and leading to resistance to enzalutamide. Consistently, SRC inhibitor dasatinib rescued enzalutamide sensitivity and inhibited the proliferation of enzalutamide-resistant cancer cells. Taken together, our findings demonstrate a substantial role for FMNL2/SRC interaction in the regulation of AR translocation, suggesting that targeting FMNL2-mediated SRC activation might be a potential therapeutic strategy for enzalutamide-resistant PCa, and dasatinib could be an option.
2025-01-13 | PXD059539 | Pride
Project description:Prostate cancer is the second leading cause of cancer death among men in the United States. The androgen receptor (AR) antagonist enzalutamide is a FDA-approved drug for treatment of patients with late-stage prostate cancer and is currently under clinical study for early-stage prostate cancer treatment. After a short positive response period to enzalutamide, tumors will develop drug resistance. In this study, we uncovered that DNA methylation was deregulated in enzalutamide-resistant cells. DNMT activity and DNMT3B expression were upregulated in resistant cell lines. Enzalutamide induced the expression of DNMT3A and DNMT3B in prostate cancer cells with a potential role of p53 and pRB in this process. The overexpression of DNMT3B3, a DNMT3B variant, promoted an enzalutamide-resistant phenotype in C4-2B cell lines. Inhibition of DNA methylation and DNMT3B knockdown induced a re-sensitization to enzalutamide. Decitabine treatment in enzalutamide-resistant cells induced a decrease of the expression of AR-V7 and changes of genes for apoptosis, DNA repair and mRNA splicing. Combination treatment of Decitabine and enzalutamide induced a decrease of tumor weight, Ki-67 and AR-V7 expression and an increase of cleaved-caspase3 levels in 22Rv1 xenografts. The collective results suggest that DNA methylation pathway is deregulated after enzalutamide resistance onset and that targeting DNA methyltransferases restores the sensitivity to enzalutamide in prostate cancer cells.
2021-09-22 | GSE184168 | GEO
Project description:Prostate cancer C4-2B cells were cultured in enzalutamide in a dose-escalation manner. After sixty passages cells were resistant to enzalutamide, with a specific sets of genes been deregulated. We performed global gene expression analysis by cDNA microarrays to identify genes responsible for enzalutamide resistance in C4-2B-MDVR cells. Enzalutamide resistant C4-2B-MDVR cells were selected from C4-2B cells during long time enzalutamide treatment. Genes responsible for enzalutamide resistance were identified using C4-2B vs. C4-2B-MDVR RNA extraction and hybridization on Affymetrix microarrays.
2015-04-09 | E-GEOD-64143 | biostudies-arrayexpress
Project description:Castration resistant prostate cancer (CRPC) develops resistance to antiandrogens affecting Androgen Receptor (AR) signaling through a variety of mechanism. Because of this, the efficacy of androgen receptor targeted therapy remains limited for many patients with CRPC. We developed C42B-enzalutamide (ENZU) and resistance cells to study changes in transcriptomic profile compared to parental cells.
2020-12-31 | GSE151083 | GEO
Project description:Illumina gene array analyses of prostate cancer cell lines that had acquired resistance to Enzalutamide (MDV3100). mRNA analyses of four cell lines (CWR-R1, LAPC-4, LNCaP, and VCAP) cells that were either untreated, treated for 48hrs with Enz (short-term), or continuously grown in Enzalutamide for >6 months.
2016-02-24 | E-GEOD-78201 | biostudies-arrayexpress
Project description:Prostate cancer is the second leading cause of cancer death among men in the United States. The Androgen receptor (AR) antagonist Enzalutamide is a FDA approved therapy for treatment of late stage prostate cancer patients and is currently under clinical study for early stage prostate cancer treatment. After a short positive response period, patients will develop drug resistance. In this study we used RNA-sequencing and bioinformatics analysis to identify Notch signaling pathway as a deregulated pathway in Enzalutamide-resistant cells. NOTCH2 and c-MYC positively correlated with AR expression in patients' samples mimicking cells with Enzalutamide-resistance. In Enzalutamide-resistant cells, MR49F and C4-2R, we found that cleaved-NOTCH1, HES1 and c-MYC protein expression are significantly elevated indicating an activated NOTCH1 pathway in those cells. In addition, ADAM10 and ADAM17 had a higher expression in Enzalutamide-resistant cells, suggesting a role for S2 cleavage in the increased cleaved NOTCH1 expression. Furthermore, treatment of Enzalutamide-resistant cells with PF-03084014 in combination with Enzalutamide increased cell death, decreased colony formation ability and re-sensitized Enzalutamide-resistant cells to Enzalutamide. Knockdown of NOTCH1 in C4-2R increases Enzalutamide sensitivity by decreasing cell proliferation and increasing cell death. In a 22RV1 xenograft model, PF-03084014 and Enzalutamide induced a decrease in tumor growth through a reduced cell proliferation and increased apoptosis. These results indicate that Notch1 signaling can contribute to Enzalutamide-resistance in Prostate cancer and inhibition of this pathway can re-sensitize resistant cells to Enzalutamide.
2019-04-01 | GSE123379 | GEO
Project description:Enzalutamide, a second-generation androgen receptor inhibitor, is utilized for treating patients with metastatic castration-resistant prostate cancer (mCRPC). However, acquired resistance to enzalutamide presents a significant clinical challenge, necessitating novel strategies for overcoming this resistance. In this study, we demonstrated that PLK1 phosphorylates PDCD4 at serine 239 (S239), leading to PDCD4 degradation by enhancing its binding to βTRCP2, thereby promoting enzalutamide resistance both in vitro and in vivo. Mechanistically, phosphorylation of PDCD4 at S239 upregulates the expression of UDP-glucuronosyltransferase 2B15 (UGT2B15) through activation of the c-MYC-Hedgehog axis. This pathway circumvents the androgen receptor, thereby reducing cellular sensitivity to enzalutamide treatment. Inhibition of UGT2B15 enhances enzalutamide-induced cell apoptosis and growth arrest in a manner dependent on PDCD4-S239 phosphorylation. Our findings provide a insight into the role of PLK1-mediated PDCD4 phosphorylation in enzalutamide resistance and suggest a potential therapeutic strategy to overcome resistance in prostate cancer.
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