Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Small Molecule Inhibitors that Disrupt the MTDH-SND1 Complex Suppress Breast Cancer Progression and Metastasis

ABSTRACT: Small Molecule Inhibitors that Disrupt the MTDH-SND1 Complex Suppress Breast Cancer Progression and Metastasis

PROVIDER: PRJNA670433 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12859841.fastq.gz	Fastqsanger.gz
	SRR12859842.fastq.gz	Fastqsanger.gz
	SRR12859843.fastq.gz	Fastqsanger.gz
	SRR12859844.fastq.gz	Fastqsanger.gz
	SRR12859845.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

Small Molecule Inhibitors that Disrupt the MTDH-SND1 Complex Suppress Breast Cancer Progression and Metastasis

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

Targeting MTDH-SND1 interaction

Project description:Targeting MTDH-SND1 interaction

| PRJNA730819 | ENA

Snd1-Mtdh interaction regulates cell survival under camptothecin-induced replication stress

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

Snd1-Mtdh interaction regulates cell survival under camptothecin-induced replication stress

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

2014-08-12 | GSE55522 | GEO

Small-molecule inhibitors that disrupt the MTDH-SND1 complex suppress breast cancer progression and metastasis.

Project description:Metastatic breast cancer is a leading health burden worldwide. Previous studies have shown that metadherin (MTDH) promotes breast cancer initiation, metastasis and therapy resistance; however, the therapeutic potential of targeting MTDH remains largely unexplored. Here, we used genetically modified mice and demonstrate that genetic ablation of Mtdh inhibits breast cancer development through disrupting the interaction with staphylococcal nuclease domain-containing 1 (SND1), which is required to sustain breast cancer progression in established tumors. We performed a small-molecule compound screening to identify a class of specific inhibitors that disrupts the protein-protein interaction (PPI) between MTDH and SND1 and show that our lead candidate compounds C26-A2 and C26-A6 suppressed tumor growth and metastasis and enhanced chemotherapy sensitivity in preclinical models of triple-negative breast cancer (TNBC). Our results demonstrate a significant therapeutic potential in targeting the MTDH-SND1 complex and identify a new class of therapeutic agents for metastatic breast cancer.

| S-EPMC8818087 | biostudies-literature

Staphylococcal Nuclease and Tudor Domain Containing protein SND1 interacts with ERG and plays a critical role in prostate cancer in vivo

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

Effects of targeting MTDH-SND1 interaction in mammary tumor cell and normal mammary epithelial cell in 3D culture in vitro

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

Staphylococcal Nuclease and Tudor Domain Containing protein SND1 interacts with ERG and plays a critical role in prostate cancer in vivo

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

The methylarginine reader function of SND1 is oncogenic

Project description:Staphylococcal nuclease Tudor domain containing 1 (SND1) protein is an oncogene that “reads” methylarginine marks through its Tudor domain. Specifically, it recognizes methylation marks deposited by protein arginine methyltransferase 5 (PRMT5), which is also known to promote tumorigenesis. SND1 is a known driver of hepatocellular carcinoma, but it is unknown if the Tudor domain is needed to drive this disease. We sought to identify the biological role of the SND1 Tudor domain in normal and tumorigenic settings. To do so, we developed two genetically engineered SND1 mouse models, namely a knockout (Snd1 KO) and a Snd1 Tudor domain mutated (Snd1 KI) mouse. Transcriptome analysis of normal KO and KI liver samples reveals a role for the SND1 Tudor domain in regulating expression of major acute phase proteins (APPs) and genes involved in the unfolded protein response (UPR), which could provide mechanistic insight into SND1’s functions in a tumor setting. These processes may provide insight into how SND1 functions as an oncogene. These results support the use of PRMT5 inhibitors, and the development of small molecule inhibitors that target the SND1 Tudor domain, as novel treatments for HCC.

2024-09-07 | GSE237559 | GEO

Cytoplasmic MTDH associates with mRNAs

Project description:To examine whether MTDH is a novel RNA binding protein and regulates either metabolism or translation of various mRNAs, we performed a RNA-binding protein immunoprecipitation (RIP) with MTDH and IgG antibodies, and the resulting immunoprecipitated RNA was subjected to a microarray to identify transcripts associating with MTDH. In addition we tested the effect of PI3K inhibition using BEZ235 (a dual PI3K/mTOR inhibitor) on the association of MTDH with target mRNAs.

2011-07-13 | GSE30588 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data