Fig. 6: Host ATF4 ablation severely impairs lung colonization and metastasis of melanoma cells.

a, Volcano plot from genome-wide gene expression microarray on lungs from Atf4WT/WT and Atf4Δ/Δ mice at 4 weeks after tamoxifen treatment (Atf4Δ/Δ versus Atf4WT/WT). b, Bar plot displaying the 15 most significantly enriched gene ontology terms in lungs from Atf4WT/WT compared with Atf4Δ/Δ mice from a. c, Box and whisker plot of the quantitative MS analysis in Atf4WT/WT and Atf4Δ/Δ lungs (nmol mg–1 of lung) for glycine and proline (n = 4 biologically independent samples per group). d, Schematic of the lung colonization experiment. Mice were injected with 1.5 × 105 B16F10 cells in the tail vein, and lungs were collected 3 weeks later. e, Representative images from Atf4WT/WT and Atf4Δ/Δ lungs. f, Box and whisker plot of the number of macroscopic lung metastases (mets) (n = 7–8 biologically independent samples per group). g, Schematic of the process to analyse metastatic activity. Mice were subcutaneously injected with 5 × 105 B16F10 cells, and the primary tumours were surgically excised when they reached about 300 mm3. The mice were sutured and followed-up for a period of 4 weeks. h, Representative images from lungs, collected 4 weeks after tumour excision. i, Box and whisker plot of the macroscopic lung metastases (n = 7–9 biologically independent samples per group). Unpaired two-sample t-test in all box and whisker plots.