Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA310695 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Chemotherapy resistance presents a major hurdle for cancer treatment. We proposed to identify the molecular changes through which breast cancer cells evolve resistance to conventional treatment, here cisplatin, so targeted therapy can be developed. Candidate approach RNAi screening was combined with cisplatin treatment in order to identify molecular pathways conferring survival advantages. The screening identified ATP7A, a copper transport ATPase responsible for the intercellular movement and sequestering of cisplatin, as a therapeutic target. Copper chelation with tetrathiomolybdate (TM) targets ATP7A. TM in combination with cisplatin sensitized drug-resistant breast cancer cells. Allograft and xenograft models in aythymic mice treated with TM/cisplatin combination therapy inhibited tumor growth and increased survival compared with monotreated mice. Examination of the molecular effects of TM on cisplatin efficacy in drug-resistant tumors revealed reduced levels of APT7A, reduced cisplatin sequestering by ATP7A and increased nuclear availability of cisplatin. Further, we showed that TM treatment combined with cisplatin reduced the half-life of ATP7A in human breast cancer cell lines. This finding offered the potential to combat drug platinum-resistant tumors and sensitize patients to conventional breast cancer treatments by identifying and targeting resistant tumors’ unique molecular adaptations.
2017-06-19 | GSE77515 | GEO
Project description:Identifying novel anti-angiogenic targets in human breast cancer
2025-01-24 | E-GEOD-31138 | ExpressionAtlas
Project description:Although three proteasome inhibitors have been used for liquid tumor treatment, their effectiveness against solid tumors remains inadequate. To address this issue, we employed a drug combination strategy and discovered that ammonium tetrathiomolybdate (TM) and AMD3100 can sensitize solid cancer cell lines to proteasome inhibitors. Mechanistically, we found that TM and AMD3100 reduce proteasome activity by decreasing the protein level of PSMB5. This reduction occurs through the activation of the AMPK pathway, which inhibits STAT3 phosphorylation. Notably, our in vivo studies revealed that drug combinations retarded tumor growth dependent on CD8+ T cells. The combination of bortezomib with TM or AMD3100 induced cancer cell antigen presentation and the production of CCL5, which together stimulated the recruitment and generation of cytotoxic CD8+ T cells. This study identifies new synergistic lethal pairs that enhance the effectiveness of bortezomib-centered therapy against breast cancer.
2025-05-01 | GSE296112 | GEO
Project description:Copper serves as a co-factor for a host of metalloenzymes that contribute to malignant progression. The orally bioavailable copper chelating agent tetrathiomolybdate (TM) has been associated with a significant survival benefit in high-risk triple negative breast cancer (TNBC) patients. Despite these promising data, the mechanisms by which copper depletion impacts metastasis are poorly understood and this remains a major barrier to advancing TM to a randomized phase II trial. Here, using two independent TNBC models, we report a discrete subpopulation of highly metastatic SOX2/OCT4+ cells within primary tumors that exhibit elevated intracellular copper levels and marked sensitivity to TM. Global proteomic and metabolomic profiling identified TM-mediated inactivation of Complex IV as the primary metabolic defect in the SOX2/OCT4+ cell population. We identified the AMPK/mTORC1 energy sensor as an important downstream pathway and show that AMPK inhibition rescues TM-mediated loss of invasion. Furthermore, loss of the mitochondria-specific copper chaperone, COX17, restricted copper deficiency to mitochondria and phenocopied TM-mediated alterations. These findings identify a novel copper-metabolism-metastasis axis with potential to enrich patient populations in next-generation therapeutic trials.
2021-10-26 | PXD027089 | Pride
Project description:Networking of differentially expressed genes in human MCF7 breast cancer cells resistant to methotrexate
2025-01-24 | E-GEOD-16070 | ExpressionAtlas
Project description:Antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells
2025-01-24 | E-GEOD-19777 | ExpressionAtlas
Project description:Networking of differentially expressed genes in human MDA-MB-468 breast cancer cells resistant to methotrexate
2025-01-24 | E-GEOD-16080 | ExpressionAtlas
Project description:Tamoxifen resistance has been a major clinical problem and is accountable for relapse in about one third of ER positive breast cancer patients. Most of the recurrent patients will eventually receive chemotherapy. However, the chemosensitivity of these tamoxifen-resistant breast cancer patients has never been explored. In this study, we demonstrate that tamoxifen-resistant breast cancer cells express significantly more BARD1 and BRCA1, which results in the resistance to DNA-damaging chemotherapy including cisplatin and adriamycin , but not to paclitaxel. Silencing BARD1 or BRCA1 expression or inhibition of BRCA1 phosphorylation by Dinaciclib restored the sensitivity to cisplatin in tamoxifen-resistant cells. In addition, we identified that activated PI3K/AKT pathway in tamoxifen-resistant cells was responsible for the upregulation of BARD1 and BRCA1. PI3K inhibitors, BKM120 and BYL719, decreased the expression of BARD1 and BRCA1 in tamoxifen-resistant cells and re-sensitized them to cisplatin both in vitro and in xenografted mice. Higher BARD1 and BRCA1 expression was associated with poor prognosis of early breast cancer patients, especially the ones received radiotherapy, indicating the potential use of PI3K inhibitors to reverse chemoresistance and radioresistance in ER positive breast cancer patients.
2021-03-15 | GSE111926 | GEO
Project description:Genes regulated by hepatocyte growth factor as targets to sensitize ovarian cancer cells to cisplatin
| PRJNA116369 | ENA
Project description:Purpose: The goal of our study is to identify the differentially expressed genes between cispaltin sensitive and cisplatin resistance gastric cancer cell line. Methods: Transcriptome sequencing of cisplatin sensitive and cisplatin resistance KATOIII cells were generated by Illumina HiSeq TM, for triplicates Results : Using an optimized data analyzed workflow, we mapped 57773 genes and were found 5966 differentially expressed genes between cisplatin sensitive KATOIII and cisplatin resistance KATO/DDP cell lines.
2021-10-22 | GSE186205 | GEO