Figure 4—figure supplement 1.
- ID
- ZDB-FIG-210218-37
- Publication
- Fazio et al., 2021 - SATB2 induction of a neural crest mesenchyme-like program drives melanoma invasion and drug resistance
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(A) Overexpression of SATB2 with TETon (iSATB2) in normal human epidermal melanocytes (HEMA-LP) and in SKMEL2, SKMEL28, and A375 melanoma cells is sufficient to induce transcriptional activation of SOX10, SNAI1/2, PDGFB, and SEMA3F mRNA. qRT-PCR Data was normalized to beta-actin, and fold change was determined compared to un-induced controls. *p<0.05, **p<0.001, ***p<0.0001, ****p<0.0001. (B) Overlap of Ingenuity Pathway Analysis and Gene Set Enrichment Analysis Hallmark pathways of RNA-seq in MCR zebrafish tumors and iSKMEL2 human (plus vs. minus doxycycline) melanoma cell line. For IPA humanized significant zebrafish genes were used (p<0.05, q < 0.05, FC>|1.5|=1044 zf->840 unique human orthologs), and significant SKMEL2 iSATB2 genes (p<0.05, q < 0.05, FC>|1|). (C) Curated heatmap of altered genes in RNA-seq of human SKMEL2 cells overexpressing SATB2 (plus DOX vs. minus DOX FC >1; p<0.01) that have been involved in neural crest or Rambow Neural crest-like state, PDGF-PDGFR-SRC invadopodia cascade, AXL/MITF state and melanocyte differentiation. All genes shown are significantly altered except for TFAP2C. Normalized RNA-seq heatmap of expression fold change Z-score is plotted. Genes part of the neural crest GRN are highlighted in blue, invadopodia related genes are highlighted in green, and MAPK inhibitors resistance genes are highlighted in magenta. (D) Gene set enrichment analysis (GSEA) of 1000 MSigDB signatures including the states described by Tirosh et al. and Rambow et al. |