Antitumor drug-induced cellular senescence in breast cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE222984 | GEO | 2023/12/08
REPOSITORIES: GEO
Similar Datasets
Project description:RNA-sequencing of senescent (doxorubicin) human melanoma SK-MEL-103 cells and human fetal lung fibroblast IMR-90 with different interventions
2024-07-15 | GSE236521 | GEO
Project description:Abstract: Cellular senescence, an integral component of aging and cancer, arises in response to diverse triggers, including telomere attrition, macromolecular damage, and signaling from activated oncogenes. At present, senescent cells are identified by the combined presence of multiple traits, such as senescence-associated protein expression and secretion, DNA damage, and β-galactosidase activity; unfortunately, these traits are neither exclusively nor universally present in senescent cells. To identify robust shared markers of senescence, we have performed RNA-sequencing analysis across 8 diverse models of senescence triggered in human diploid fibroblasts (WI-38, IMR-90) and endothelial cells (HUVEC, HAEC) by replicative exhaustion, exposure to ionizing radiation or doxorubicin, and expression of the oncogene HRASG12V. The intersection of the altered transcriptomes revealed 47 RNAs consistently elevated and 26 RNAs consistently reduced across all senescence models, including many protein-coding mRNAs and some long noncoding RNAs. We propose that these shared transcriptome profiles will enable the identification of senescent cells in vivo, the investigation of their roles in aging and malignancy, and the development of strategies to target senescent cells therapeutically.
2019-06-12 | GSE130727 | GEO
Project description:This experiment follows the transcriptional response of human fibroblasts (BJ) to two different drug treatments (doxorubicin and abemaciclib) in comparison to treatment with vehicle (water). The two drugs are used in cancer care and their mechanism of action entails proliferative arrest. Doxorubicin is a member of the anthracycline family and acts as a topoisomerase II inhibitor. Abemaciclib is an inhibitor of the Cyclin Dependent Kinases (CDK) 4/6 which arrest cell cycle at the G1/S phase.
2021-11-29 | E-MTAB-7642 | biostudies-arrayexpress
Project description:The purpose of this study was to determine whether leukemia cells can escape from drug-induced senescence; determine the phenotype of the senescent, and escaped cells, and whether senescent leukemia cells can be specifically eliminated prior to their escape. Methods: DA3/EPOR cells were treated with 200ng/ml doxorubicin for 24 hr. Cells were confirmed to enter and exit senescence based on, proliferating and SA-gal staining. mRNA transcriptional profiles of naïve proliferating, senescent, and escaped DA3/EPOR murine leukemia cells were generated by deep sequencing, in biological triplicate, using Illumina NovaSeq 6000 at a depth of 25 million pair-ended reads that were 100 bp in length. The sequence reads that passed quality filters, the first 13 nucleotides were removed from each read. Alignment to the MM10 indexed genome was done using HiSAT2. Read counts were genereated using HTSEQ, which were then used for differential expression. Differential expression was performed on Rstudio using EdgeR. qRT–PCR was performed for validation. Results: We report that DA3/EPOR leukemia cells enter and escape a doxorubicin (Dox)-induced senescence, dependent on erythropoietin (EPO). EPO is necessary for DA3/EPOR cells to survive the senescent state. Senescent DA3/EPOR cells undergo a transcriptional reprogramming, which is largely reversible upon escape. Escaped DA3/EPOR cells mirror naïve, never senescent DA3/EPOR cell, and respond similarly to Dox. Senescent DA3/EPOR cells mimic a diapause-like state, and undergo metabolic changes. Senescent DA3/EPOR cells and some drug-induced senescent human acute myeloid leukemia (AML) cells can be eliminated with chloroquine, a lysosome inhibitor. Lastly, we show with The Cancer Genome Atlas publicly available data that the senescent signature is associated with decreased survival in AML and multiple other cancers. Conclusion: Leukemia cells persist through drug treatment by entering a reversible senescent state that mimics diapause. Senescent leukemia cells depend on lysosome activity to persist, and treatment with chloroquine, a lysosome inhibitor, can eliminate senescent leukemia cells.
2023-08-09 | GSE186200 | GEO
Project description:The aim of the present study was to provide a comprehensive characterization of whole genome DNA methylation patterns in replicative and ionizing irradiation- or doxorubicin-induced premature senescence, exhaustively exploring epigenetic modifications in three different human cell types: in somatic diploid skin fibroblasts and in bone marrow- and adipose-derived mesenchymal stem cells. With CpG-wise differential analysis three epigenetic signatures were identified: a) cell type- and treatment-specific signature; b) cell type-specific senescence-related signature; and c) cell type-transversal replicative senescence-related signature. Cluster analysis revealed that only replicatively senescent cells created a distinct group reflecting notable alterations in the DNA methylation patterns accompanying this cellular state. Replicative senescence-associated epigenetic changes seemed to be of such an extent that they surpassed interpersonal dissimilarities. Enrichment in pathways linked to the nervous system and involved in the neurological functions was shown after pathway analysis of genes involved in the cell type-transversal replicative senescence-related signature. Although DNA methylation clock analysis provided no statistically significant evidence on epigenetic age acceleration related to senescence, a persistent trend of increased biological age in replicatively senescent cultures of all three cell types was observed. Overall, this work indicates the heterogeneity of senescent cells depending on the tissue of origin and the type of senescence inducer that could be putatively translated to a distinct impact on tissue homeostasis.
2023-03-20 | GSE227160 | GEO
Project description:Breast cancer cells and two metaplastic breast cancer cell lines were used: a widely available, HS578T, and a novel line isolated from a metaplastic breast cancer tumor, BAS. Doxorubicin and paclitaxel resistant derivatives of these metaplastic lines were generated and miR profiling performed.
2023-01-29 | GSE144445 | GEO
Project description:Two metaplastic breast cancer cell lines were used: a widely available, HS578T, and a novel line isolated from a metaplastic breast cancer tumor, BAS. Doxorubicin and paclitaxel resistant derivatives of these lines were generated and transcriptome profiling performed.
2023-01-23 | GSE144113 | GEO
Project description:Among the different chemotherapies available, genotoxic drugs are widely used. In response to these drugs, particularly doxorubicin, tumor cells can enter into senescence. Chemotherapy-induced senescence (CIS) is a complex response. Long described as a definitive arrest of cell proliferation, we and various groups have shown that this state may not be complete and could allow certain cells to reproliferate. The mechanism could be due to the activation of new signaling pathways. In the laboratory, we study the proteins involved in these pathways and triggering cell proliferation. In this study, we determine a new role for Anterior Gradient protein 2 (AGR2) in vivo in patients and in vitro in a senescence escape model. We used proteomic studies of patients’ samples and cell lines, and also RNA interference to assess the implication of AGR2 in breast cancer and proliferation of senescent cells. First, we identified AGR2, and found that its concentration is higher in the serum of breast cancer patients and that this high concentration is associated with metastasis occurrence. We also observed an inverse correlation between intratumoral AGR2 expression and the senescence marker p16. This observation led us to study AGR2’s role in the CIS escape model. In this model, we found that AGR2 is overexpressed in cells during senescence escape and its loss considerably reduces that phenomenon. Furthermore, we showed that the extracellular form eAGR2 stimulated the reproliferation of senescent cells. The power of proteomic analysis based on the SWATH-MS approach allowed us to highlight the mTOR/AKT signaling pathway in the senescence escape mechanism mediated by AGR2. Analysis of the two signaling pathways revealed that AGR2 modulates RICTOR phosphorylation. All these results show that AGR2 is a breast cancer biomarker and regulates CIS escape via activation of the mTORC2/AKT signaling pathway.
2022-02-15 | PXD028073 | Pride
Project description:We measured changes in chromatin accessibility after treatment of human breast cancer cell lines with abemaciclib
2020-08-31 | GSE157082 | GEO
Project description:We measured changes in gene expression after treatment of human breast cancer cell lines with abemaciclib.
2020-09-03 | GSE157383 | GEO