Project description:CADM1 expression in non-adherent conditions was found to potently induce caspase-independent cell death. We sought to use microarray analysis to glean insights to the mechanism associated with CADM1 induced non-adherent cell death.
Project description:The circadian clock regulator Bmal1 modulates tumorigenesis, but its reported effects are often inconsistent. Here, we show that Bmal1 has a context-dependent role in mouse melanoma tumor growth. Loss of Bmal1 in YUMM or B16 melanoma cells eliminated clock function, and diminished hypoxic gene expression signature and tumorigenesis, which could be rescued by ectopic expression of HIF-1a. By contrast, over-expressed wild-type or a dominant negative Bmal1 non-canonically sequestered myosin heavy chain 9 (Myh9) to increase MRTF-SRF activity and AP-1 transcriptional signature, and shift YUMM 2.1 cells from a Sox10high to a Sox9high immune resistant, mesenchymal cell state that is found in human melanomas. Our work uncovers a link between Bmal1, Myh9, mouse melanoma cell plasticity, and tumor immunity. This connection may underlie cancer therapeutic resistance and underpin the link between the circadian clock, MRTF-SRF and the cytoskeleton.
Project description:SALL4 builds a complex with histone deacetylases, and is thought to confer its effects epigenetically. Both loss of Sall4 and inhibition of HDAC2 leads to an invasiveness in human melanoma cells. To study co-occupancy of SALL4 and HDAC2, we employed CUT&RUN targeting SALL4 and HDAC2 in human melanoma cells (M010817).
Project description:Recently it was found that dipotassium-trioxohydroxytetrafluorotriborate, K2(B3O3F4OH), is a potent and highly specific inhibitor of precancerous cell processes. We conducted gene expression profiling of human melanoma cells before and after treatment with two concentrations (0.1 and 1 mM) of this boron inorganic derivative in order to assess its effects on deregulation of genes associated with tumor pathways. Parallel trypan blue exclusion assay was performed to assess the cytotoxicity effects of this chemical. Treatment with K2(B3O3F4OH) induced a significant decrease of cell viability in melanoma cellline at both tested concentrations. Furthermore, these treatments caused deregulation of more than 30 genes known as common anti-tumor drug targets. IGF-1 and hTERT were found to be significantly downregulated and this result may imply potential use of K2(B3O3F4OH) as an inhibitor or human telomerase and insulin-like growth factor 1, both of which are associated with various tumor pathways.
Project description:LC-MS/MS targeted files submitted as support material for the paper: Quantitative mass spectrometry analysis of PD-L1 protein expression, N-glycosylation and expression stoichiometry with PD-1 and PD-L2 in human melanoma.
Project description:Specifically, we report that drug-insensitive melanoma cells can maintain higher levels of antioxidant metabolites to withstand the lethal effects of drugs. By extending our analysis to other melanoma subtypes in the TCGA, we show that elevated redox capacity could indeed be a general feature of melanoma. Our results suggest that redox vulnerabilities could be exploited for therapeutic benefits and identify unsuspected combination targets to enhance the effects of BRAFi in pan-melanoma.
Project description:The genetic changes underlying metastatic melanoma need to be deciphered to develop new and effective therapeutics. Previously, genome-wide microarray analyses of human melanoma identified two reciprocal gene expression programs, that included expression of mRNAs regulated by either transforming growth factor, beta 1 (TGFB1) pathways or microphthalmia-associated transcription factor (MITF)/SRY-box containing gene 10 (SOX10) pathways. We extend this knowledge to include gene expression analyses of 5 additional human melanoma lines, and show that these lines also fall into either TGFB1 or MITF/SOX10 gene expression groups. These mRNA expression studies were followed up by miRNA expression analyses.
Project description:We report the gene expression comparison of human A375 melanoma cells with GDF6 and BMP pathway modulation. These comparisons were used to determine the gene signature regulated by GDF6.
Project description:Human melanoma A2058 cells were transfected with PARP1 siRNA or control siRNA for 48 and 72 h. Goal was to determine the effects of PARP1 on global A2058 gene expression by comparing the changes in the expression profile of melanoma cells after PARP1 interference.