Fig. 4

a. HOMER de-novo motif analysis on genes upregulated in ZMEL1-PRO vs. -INV (log₂ fold change cutoff ± 1.5, p_adj < 0.05, ±500bp of transcription start site [TSS]). b. HOMER de-novo motif analysis of genes differentially expressed between ZMEL1-INV in 3D (clusters) vs. 2D (no clusters) (log₂ fold change cutoff ± 1.5, p_adj < 0.05, ±500bp of TSS). c. Cluster size after 2 days in ZMEL1-PRO with CRISPR-Cas9 inactivation of tfap2a and tfap2e alone or in combination (sg_tfap2a/e) versus control (sg_scr) (p-values by linear regression; N=3 independent experiments). d. Representative images of clusters formed after 2 days from ZMEL1-PRO with sg_scr vs. sg_tfap2a/e. e. Growth of ZMEL1-PRO orthotopic primary tumors with sg_scr vs. sg_tfap2a/e (p=0.011 by linear regression; N=3 independent experiments with sg_scr/sg_tfap2a/e 24/22, 22/22, 24/24 fish per group, respectively; n=138 fish total). f. Representative composite image of extravasated (arrows) and partially extravasated (arrow-head) ZMEL1-PRO cells with sg_tfap2a/e following intravenous transplant in casper fish with kdrl-RFP transgene labeling the vasculature. g. Proportion of larval fish intravenously transplanted with ZMEL1-PRO with sg_scr or sg_tfap2a/e with extravasated cells at 1 dpt, as quantified from confocal time lapse microscopy (OR [95% CI]: 2.20 [1.05, 4.61]; p=0.038 by logistic regression; N=3 independent experiments with sg_scr/sg_tfap2a/e 20/20, 22/23, and 22/22 fish per group, respectively; n=129 fish total). See also Figure S4 and Tables S2,S3.