Effect of depletion of CDK4 on gene expression of MCF-7 breast cance cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1089108 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28372623_1.fastq.gz | Fastqsanger.gz | |||
| SRR28372623_2.fastq.gz | Fastqsanger.gz | |||
| SRR28372624_1.fastq.gz | Fastqsanger.gz | |||
| SRR28372624_2.fastq.gz | Fastqsanger.gz | |||
| SRR28372625_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:CDK4/6 inhibitors act as a cytostatic by targeting CDK4/6-cyclin D, and have achieved great success in hormone receptor-positive breast cancer treatment. Beyond cell cycle signaling pathway, recent research on non-cell cycle related functions of CDK4/6 has been blooming. Insights in this field may expand the therapeutic benefits of CDK4/6 inhibitors. Here, we attempt to explore the effects of CDK4/6 inhibitors on breast cancer from the perspective of epigenetic modifications, especially histone modifications, through high-throughput proteomic and genomics approaches. We reveal that inhibition of CDK4 directly suppresses phosphorylation of p300, an acetyltransferase, stimulates its ubiquitin degradation, and down-regulates the histone H3K27ac. Then, p300-mediated transcriptionally inhibition of BRCA1 and enrichment of breast cancer stem cells (BCSC) gene signatures lead to the increase of the proportion of ALDH1+ breast CSCs in ER+ breast cancer after long treatment with CDK4/6 inhibitors in vitro and in vivo. our results reveal a novel phosphorylation substrate of CDK4/cyclin D complex, and offer an unrecognized side effect of CDK4/6 inhibitors, inducing stem cell properties in ER+ breast cancer.
2024-09-17 | GSE261797 | GEO
Project description:TRIM3 depletion in MCF-7 cells
| PRJNA601105 | ENA
Project description:Neurofibromin/NF1-depletion (NF1low) is associated with endocrine therapy resistance in approximately 20% of ER+/HER2– early-stage breast cancer but specific treatments for NF1low tumors are not established. Proteogenomic analyses on ER+/HER2– breast cancer demonstrated that NF1low tumors exhibit elevated CDK4/6 activity. NF1-silencing in cell lines promoted ER recruitment to CCND1, thus increasing cyclin-D1 levels. Additionally, RAF is demonstrated to directly phosphorylate the CDK4 activation-loop (pT172) thus providing a direct connection between NF1 loss and an increase in CDK4 activity. Consequently, NF1low cancer cells are differentially sensitive to a fulvestrant plus CDK4/6 inhibitor (CDK4/6i) combination, with cell-death induction in vitro, and durable tumor regressions in ER+ NF1low PDX models in vivo. Furthermore, NF1low ER+/HER2– tumors treated neoadjuvantly with 4 weeks of anastrozole exhibited a minimal reduction of a multigene mRNA proliferation score vs NF1high tumors but exhibited marked sensitivity to the subsequent addition of palbociclib. In conclusion, dual ER and downstream RAF activation following NF1-loss drives endocrine therapy resistance and CDK4/6i sensitivity in NF1low ER+ breast cancer. NF1 status should therefore be prioritized for biomarker investigations in adjuvant CDK4/6i trials to determine whether the NF1low status
2025-12-15 | PXD052290 | Pride
Project description:CDK4/6 inhibition is the standard of care for estrogen receptor positive (ER+) breast cancer, although cytostasis is frequently observed, and new treatment strategies that enhance efficacy are required. We performed a genome-wide CRISPR screen to identify genetic determinants of CDK4/6 inhibitors sensitivity. Multiple genes involved in oxidative stress and ferroptosis modulated palbociclib sensitivity. Depletion or inhibition of GPX4 increased sensitivity to palbociclib in ER+ breast cancer models, and sensitised triple negative breast cancer models to palbociclib, with GPX4 null xenografts being highly sensitive to palbociclib. Palbociclib induced oxidative stress and disordered lipid metabolism with lipid peroxidation, leading to a ferroptosis-sensitive state. Lipid peroxidation relied on a peroxisome AGPAT3-dependent pathway in ER+ breast cancer models, rather than the classical ACSL4 pathway. Our data demonstrate that CDK4/6 inhibition creates vulnerability to ferroptosis that could be exploited through combination with GPX4 inhibitors, enhancing sensitivity to CDK4/6 inhibition in breast cancer.
2023-06-20 | PXD043133 | Pride
Project description:RNF31 is atypical E3 ligase, which is highly expressed in human breast cancers. In order to understand the effect of RNF31 depletion effect in breast cancers, we knocked down the expression of RNF31 in MCF-7 cells. We aim to find the significantly changed pathways and cell biology behavior. 100uM RNF31 siRNA was applied to transfect the MCF-7 cells, while 100uM siControl was used as the control. Cells were cultured in DMEM red medium with 10% of FBS. Seventy two hours of post transfection, the total RNA was extracted to perform RNA expression analysis.
2014-02-06 | E-GEOD-46010 | biostudies-arrayexpress
Project description:JMJD2B is expressed in a high proportion of human breast tumors, and the expression levels significantly correlate with estrogen receptor (ER) positivity. To assess the effect of JMJD2B depletion on the ER signaling pathway, we performed genome-wide gene expression analysis using the Affymetrix Human Gene 1.0 ST array. RNA was extracted from steroid-depleted control MCF-7 cells (control E2(-)), control MCF-7 cells treated with E2 (control E2(+)), steroid-depleted JMJD2B-depleted MCF-7 cells (siJ2B E2(-)), and JMJD2B-depleted MCF-7 cells treated with E2 (siJ2B E2(+)).
2010-12-31 | E-GEOD-23445 | biostudies-arrayexpress
Project description:Neurofibromin/NF1-depletion (NF1low) is associated with endocrine therapy resistance in approximately 20% of ER+/HER2– early-stage breast cancer but specific treatments for NF1low tumors are not established. Proteogenomic analyses on ER+/HER2– breast cancer demonstrated that NF1low tumors exhibit elevated CDK4/6 activity. NF1-silencing in cell lines promoted ER recruitment to CCND1, thus increasing cyclin-D1 levels. Additionally, RAF is demonstrated to directly phosphorylate the CDK4 activation-loop (pT172) thus providing a direct connection between NF1 loss and an increase in CDK4 activity. Consequently, NF1low cancer cells are differentially sensitive to a fulvestrant plus CDK4/6 inhibitor (CDK4/6i) combination, with cell-death induction in vitro, and durable tumor regressions in ER+ NF1low PDX models in vivo. Furthermore, NF1low ER+/HER2– tumors treated neoadjuvantly with 4 weeks of anastrozole exhibited a minimal reduction of a multigene mRNA proliferation score vs NF1high tumors but exhibited marked sensitivity to the subsequent addition of palbociclib. In conclusion, dual ER and downstream RAF activation following NF1-loss drives endocrine therapy resistance and CDK4/6i sensitivity in NF1low ER+ breast cancer. NF1 status should therefore be prioritized for biomarker investigations in adjuvant CDK4/6i trials to determine whether the NF1low status identifies a particularly sensitive subset where CDK4/6i therapy is critical.
2025-05-27 | GSE273881 | GEO
Project description:Application of Next-generation sequencing technology to identify genes modulated by HOXB2 depletion in MCF-7 cells
2026-02-01 | GSE316581 | GEO
Project description:RNF31 is atypical E3 ligase, which is highly expressed in human breast cancers. In order to understand the effect of RNF31 depletion effect in breast cancers, we knocked down the expression of RNF31 in MCF-7 cells. We aim to find the significantly changed pathways and cell biology behavior.
2014-02-06 | GSE46010 | GEO
Project description:Endocrine therapy in combination with CDK4/6 inhibition doubles the progression-free survival of patients with advanced ER+ breast cancer, but resistance is inevitable, leaving patients with limited treatment options. Here, we performed unbiased genome-wide CRISPR/Cas9 knockout screens using ER+ breast cancer cells to identify novel drivers of resistance to combination endocrine therapy (tamoxifen) and CDK4/6 inhibitor (palbociclib) treatment. Our screens identified the inactivation of JNK signalling, including loss of the kinase MAP2K7, as a key driver of combination resistance. We developed multiple CRISPR/Cas9 knockout ER+ breast cancer cell lines (MCF-7 and T-47D) to investigate the effects of MAP2K7 and downstream MAPK8 and MAPK9 loss. MAP2K7 knockout increased metastatic burden in vivo and led to impaired JNK-mediated stress responses, as well as promoting cell survival and reducing senescence entry following endocrine therapy and CDK4/6 inhibitor treatment. Mechanistically, this occurred via loss of the AP-1 transcription factor c-JUN, leading to an attenuated response to combination endocrine therapy plus CDK4/6 inhibition. Furthermore, we analysed ER+ advanced breast cancer patient cohorts and found that inactivation of the JNK pathway was associated with increased metastatic burden, and low pJNKT183/Y185 activity correlated with a poorer response to systemic endocrine and CDK4/6 inhibitor therapies. Overall, we demonstrate that suppression of JNK signalling enables persistent growth during combined endocrine therapy and CDK4/6 inhibition. Our data provide a pre-clinical rationale to screen patients’ tumours for JNK signalling deficiency prior to receiving combined endocrine therapy and CDK4/6 inhibition.
2025-08-27 | GSE289411 | GEO