Snd1-Mtdh interaction regulates cell survival under camptothecin-induced replication stress
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE55522 | GEO | 2014/08/12
SECONDARY ACCESSION(S): PRJNA239832
REPOSITORIES: GEO
Similar Datasets
Project description:PyMT tumor cells with indicated status of Mtdh and Snd1 were treated with camptothecin (CPT) and the transcirptome profiles were determined and compared two sets of experiments: (1) vector control vs Snd1-KD under CPT treament (2) PyMT/Mtdh-KO cells reconstituted with either WT or Snd1-binding deficient mutant Mtdh (W391D) under CPT treatment
2014-08-12 | E-GEOD-55522 | biostudies-arrayexpress
Project description:Targeting MTDH-SND1 interaction
| PRJNA730819 | ENA
Project description:Therapeutic targeting MTDH-SND1 interaction Suppresses Breast Cancer Progression and Metastasis (GSE159764). To further elucidate the tumor intrinsic effects of the targeting and the adverse effects on normal mammary epithelial cells Mouse mammary tumor cells and normal mammary epithelial cells were isolated from transgenic mouse models and cultured in vitro 3D spheroids system. MMTV-PyMT tumor cells from cKO mouse in tumorsphere culture were treaed with tamoxifen to induce Mtdh KO, and compared to the mock treatment which maintain wild type Mtdh. Thus the tumor intrinsic effects can be determined Normal mammary epithelial cells were isolated from mouse mammary gland and cultured in vitro in mammosphere. The cells were treated with inhibitor C26A6 vs control and thus the adverse effects on normal MECs can be determined.
2021-09-07 | GSE174622 | GEO
Project description:Previous studies discovered that MTDH frequently amplifies and overexpresses in breast cancer in human patients and is strongly associated with higher metastasis and treatment failure and thereby leads to poor prognosis. In mouse mammary tumor models, knockout of Mtdh substantially reduces tumor incidence and suppresess metastasis. Furthermore, Mtdh interact with Snd1 and the interaction appears essential for its tumor promoting function. To develop novel therapeutics targeting Mtdh function, small molecular compound to disrupt the Mtdh-Snd1 interaction was identified by high throughput screen. To further elucidate the mechanism of MTDH targeting caused anti-tumor activity and to confirm the action mode of the small molecular compound C26A6 as a Mtdh-Snd1 disruptor, transcriptome changes in mouse mammary tumors following treatments of C26A6 and acute induction of Mtdh knockout by Tamoxifen treatment were investigated using next generation sequencing.
2021-09-07 | GSE159764 | GEO
Project description:ERG is a transcriptional factor, which is recombined with promoter of TMPRSS2 and prominently overexpressed in half of human prostate cancers. The mechanisms of ERG-mediated oncogenesis are not completely understood. We performed an unbiased Mass Spectrometry screen for ERG-binding proteins and found that ERG binds to MTDH/SND1 protein complex in prostate cancer cells. We determined that ERG binds to the SND1/MTDH protein complex via SND1 and this interaction plays a critical role in ERG-mediated cancer.
2023-03-22 | PXD036882 | Pride
Project description:Pharmacogenomic identification of targets for adjuvant therapy with the topoisomerase poison camptothecin. The response of tumor cells to the unusual form of DNA damage caused by topoisomerase poisons such as camptothecin (CPT) is poorly understood, and knowledge regarding which drugs can be effectively combined with CPT is lacking. To better understand the response of tumor cells to CPT and to identify potential targets for adjuvant therapy, we examined global changes in mRNA abundance in HeLa cells after CPT treatment using Affymetrix U133A GeneChips, which include all annotated human genes (22,283 probe sets). Statistical analysis of the data using a Bayesian/Cyber t test and a modified Benjamini and Hochberg correction for multiple hypotheses testing identified 188 probe sets that are induced and 495 that are repressed 8 h after CPT treatment at a False Discovery Rate of <0.05 and a minimum 3-fold change. This pharmacogenomic approach led us to identify two pathways that are CPT induced: (a) the epidermal growth factor receptor; and (b) nuclear factor-kappaB-regulated antiapoptotic factors. Experiments using HeLa cells in our lab and prior animal model studies performed elsewhere confirm that inhibitors of these respective pathways super-additively enhance CPT's cytotoxicity, suggesting their potential as targets for adjuvant therapy with CPT. Cancer Res. 2004 Mar 15;64(6):2096-104 Keywords = HeLa Keywords = Camptothecin Keywords: ordered
2004-05-18 | GSE1417 | GEO
Project description:SND1 and its partner MTDH promote cancer and therapeutic resistance; however, the mechanisms responsible for their function and potential cooperation with other oncogenes are not completely understood. We report here that oncoprotein ERG binds to the SND1/MTDH protein complex via the Tudor domain of SND1. ERG is an ETS-domain transcriptional factor, which is recombined and overexpressed in approximately half of human prostate cancers. siRNA-mediated knockdowns and CRISPR-Cas9-mediated knockout of SND1 in human prostate epithelium cell lines revealed a critical role of SND1 in proliferation of ERG-overexpressing prostate epithelial cells. Transcriptional analysis of ERG-positive human prostate cancer cells demonstrated significant overlap between genes regulated by ERG and SND1. Mechanistically, we found that ERG promoted nuclear localization of SND1/MTDH. Significantly, forced nuclear localization of SND1 by addition of exogenous nuclear localization sequences (NLS) prominently increased its growth promoting function irrespective of the status of ERG expression. To determine if SND1 is necessary for prostate cancer tumorigenesis in vivo, we generated mice with prostate-epithelium-specific deletion of Snd1. We found that inactivation of Snd1 did not impact normal prostate gland homeostasis. However, prostate epithelium-specific deletion of Snd1 in autochthonous mouse model of prostate cancer (PB-Cre/ERG/PTENflox/flox mice) showed greatly reduced invasive cancer growth and tumor burden. Moreover, gene expression analysis revealed a significant overlap between in vivo prostate transcriptional signatures of ERG and Snd1. We conclude that SND1 plays a critical role in prostate tumorigenesis and targeting SND1 may represent a potential therapeutic target in prostate cancer.
2023-09-11 | GSE212840 | GEO
Project description:DNA Topoisomerase I inhibition by Camptothecin (CPT) derivatives can impair the hypoxia-induced cell transcriptional response. In the present work, we determined molecular aspects of the mechanism of CPT effects on HIF-1alpha activity in human cancer cells. In particular, we provide evidence that low concentrations of CPT, without interfering with HIF-1alpha mRNA levels, can reduce HIF-1alpha protein expression and activity. As luciferase assays demonstrated the involvement of the HIF-1alpha mRNA 3M-^RUTR in CPT-induced impairment of HIF-1alpha protein regulation, we performed microarray analysis to identify CPT-induced modification of miRNAs targeting HIF-1alpha mRNA under hypoxic-mimetic conditions. The selected miRNAs were then further analyzed demonstrating a role for miR-17-5p and miR-155 in HIF-1alpha protein expression after CPT treatments. The present findings establish miRNAs as key factors in a molecular pathway connecting Top1 inhibition and human HIF-1alpha protein regulation and activity, widening the biological and molecular activity of CPT derivatives and the perspective for novel clinical interventions.
2013-12-02 | E-MTAB-2022 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-09-07 | GSE174630 | GEO
Project description:The anti-cancer drug camptothecin inhibits replication and transcription by trapping DNA topoisomerase I (Top1) covalently to DNA in a M-bM-^@M-^\cleavable complexM-bM-^@M-^]. To examine the effects of camptothecin on RNA synthesis genome-wide we used Bru-Seq and show that camptothecin treatment affected transcription initiation, elongation, termination, splicing and enhancer activity. Following removal of camptothecin, transcription spread as a wave from the 5M-bM-^@M-^Y-end of genes with no recovery of transcription apparent from RNA polymerases stalled in the body of genes. As a result, camptothecin preferentially inhibited the expression of large genes such as proto-oncogenes, and anti-apoptotic genes while smaller ribosomal protein genes, pro-apoptotic genes and p53 target genes showed relative higher expression. In addition, a set of mitotic regulator genes and histone genes were inhibited in a size-independent manner. Cockayne syndrome group B fibroblasts showed a very similar RNA synthesis recovery profile to normal fibroblasts suggesting that transcription-coupled repair is not involved in the repair of transcription-blocking TOP1 lesions. These findings of the effects of camptothecin on transcription have important implications for its anti-cancer activities and may aid in the design of improved combinatorial treatments involving Top1 poisons. Analysis of the effect of Camptothecin (CPT) on transcription. Normal fibroblasts and Cockayne syndrome group B fibroblasts were exposed to CPT for 60 minutes, after which a washout was performed. Nascent RNA was labeled using bromouridine for 15 minutes starting at time points: 1) 15 minutes before the washout; 2) Immediately after the washout; 3) 15 minutes after the washout. Test samples are compared to control cells that were not exposed to CPT.
2013-10-29 | E-GEOD-48678 | biostudies-arrayexpress