Dpep Inhibits Cancer Cell Growth and Survival via Shared and Context-Dependent Transcriptome Perturbations
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PROVIDER: S-EPMC10669862 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Project description:Dpep is a cell-penetrating peptide targeting transcription factors ATF5, CEBPB and CEBPD that selectively promotes apoptotic death of multiple tumor cell types in vitro and in vivo. To better understand its mechanism of action, we compared transcriptomes of 6 cancer cell lines of varying origins before and after Dpep exposure. This revealed a context-dependent pattern of regulated genes that was unique to each line, but that exhibited a number of shared elements with other lines. This included upregulation of pro-apoptotic genes and tumor suppressors as well as enrichment of genes associated with responses to hypoxia and interferons. Downregulated transcripts included oncogenes and dependency genes and enriched genes associated with different phases of the cell cycle as well as with DNA repair. In each case, such changes have the potential to lie upstream of apoptotic cell death. We also detected regulation of unique as well as shared sets of transcription factors in each line, suggesting that Dpep may initiate a cascade of transcriptional responses that culminate in cancer cell death. Such death thus appears to reflect context-dependent, yet shared disruption of multiple cellular pathways as well as of individual survival-relevant genes.
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Project description:DPEP INHIBITS CANCER CELL GROWTH AND SURVIVAL VIA SHARED AND CONTEXT-DEPENDENT TRANSCRIPTOME PERTURBATIONS
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