Abstract We have performed a functional in vivo mutagenesis screen to identify genes that, when altered, cooperate with a heterozygous Pten mutation to promote prostate tumour formation. Two genes, Bzw2 and Eif5a2 , which have been implicated in the process of protein translation, were selected for further validation. Using prostate organoid models, we show that either Bzw2 downregulation or EIF5A2 overexpression leads to increased organoid size and in vivo prostate growth. We show that both genes impact the PI3K …

<p>Supplementary File comprising of Supplementary Material and Methods, Supplementary References and Supplementary Figures S1-S7. Figure S1: IHC of melanoma and proliferation markers; Figure S2: Images of fish used for bulk RNA-seq, Figure S3: Heatmaps of most variable genes and MITF target genes; Figure S4: describes transcriptome comparison of the three melanoma models; Figure S5: apoptosis at the site of melanoma regression; Figure S6: fish used for low cell number and single cell RNA-seq; Figure S7: MITF…

<p>Supplementary file comprising Supplementary Tables S1-S8. Table S1: list of antibodies used in this study; Table S2: gene set from literature used for pathway analysis; Table S3: list of significantly enriched pathways from GSEA analysis between primary tumour and regression site (low cell number RNA-seq); Table S4: qPCR primers used in this study; Tables S5: list of shared upregulated pathways in superficial melanoma and low MITF patients; Table S6: list of shared upregulated pathways in nodular melanoma…

<div>Abstract<p>The melanocyte-inducing transcription factor (MITF)–low melanoma transcriptional signature is predictive of poor outcomes for patients, but little is known about its biological significance, and animal models are lacking. Here, we used zebrafish genetic models with low activity of Mitfa (MITF-low) and established that the MITF-low state is causal of melanoma progression and a predictor of melanoma biological subtype. MITF-low zebrafish melanomas resembled human MITF-low melanomas and we…

<div>Abstract<p>The melanocyte-inducing transcription factor (MITF)–low melanoma transcriptional signature is predictive of poor outcomes for patients, but little is known about its biological significance, and animal models are lacking. Here, we used zebrafish genetic models with low activity of Mitfa (MITF-low) and established that the MITF-low state is causal of melanoma progression and a predictor of melanoma biological subtype. MITF-low zebrafish melanomas resembled human MITF-low melanomas and we…