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SRP110248
Homo sapiens
30 Downloadable Samples
Illumina HiSeq 2000
Description
Small ubiquitin-like modifier (SUMO) family proteins regulate target protein functions by post-translational modification. However, a potent and selective inhibitor to target the SUMO pathway has been lacking. Here we describe ML-792, the first mechanism-based SUMO-activating enzyme (SAE) inhibitor with nanomolar potency in cellular assays. ML-792 selectively blocks SAE enzyme activity and total SUMOylation, which leads to reduced cancer cell proliferation. Moreover, induction of the MYC oncogene increased the ML-792 mediated viability effect in cancer cells, indicating potential application of SAE inhibitors in MYC-amplified tumors. Using ML-792, we further explored the critical roles of SUMOylation in mitotic progression and chromosome segregation. Furthermore, expression of an SAE catalytic subunit (UBA2) mutant S95N/M97T rescued SUMOylation loss and the mitotic defect induced by ML-792, confirming the selectivity of ML-792. As a potent and selective SAE inhibitor, ML-792 provides rapid loss of endogenously SUMOylated proteins allowing for novel insights into SUMO biology. Overall design: RNA-SEQ was used to analyze changes in mRNA profiles of human colon and breast cancer cells treated with ML00754792 SAEi
Publication Title
Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor.
Sample Metadata Fields
Cell line, Treatment, Subject, Time
View Samples- Homo sapiens
- 188 Downloadable Samples
- Illumina HiSeq 2500
Description
To understand the interplay between cancer and stroma, we performed single cell RNA-sequencing of PDAC cells admixed with stromal fibroblasts and defined different single cell populations with varying levels of proliferative and metastatic transcriptional states. PDAC cell behavior in vitro and in vivo on these phenotypic axes could be tuned with the proportion of stromal fibroblasts. These cell types were identified in human pancreatic tumors, and specific subpopulations were associated with worsened outcomes. Overall design: 92 single PDAC cells and 92 single CAF cells were micromanipulated and prepared for sequencing (23 of each cell type from four culture ratios). The 24th sample from each cell type-culture condition combination is a population control obtained by micromanipulating 100 cells of the given type from the given culture condition and preparing it as if it were a single cell, giving a total of 96 PDAC samples and 96 CAF samples. During the course of library construction, 3 samples were lost, all PDAC cells from the 30:70 condition (two single cells and the population control), leaving 93 total PDAC samples and 96 total CAF samples.
Publication Title
Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples