Fig. 7: High ATF4 levels or ATF4-dependent gene expression correlate with increased COL1 expression or deposition in human tumours.

The ISR gene signature comprising 32 genes was used as a surrogate for ATF4 activation. a, Pearson’s correlation between the ISR target signature and COL1A1, ACTA2, PDGFRB and FAP in SKCM and PAAD. The linear regression lines along with 95% confidence intervals (shaded regions) are shown. b, Human melanoma tissue arrays containing sections from 176 tumours and 16 healthy controls were stained for COL1 (top) and ATF4 (bottom) proteins. Damaged or tissues expressing high melanin levels were excluded from the quantification. Red and green boxes indicate representative high and low expression levels of COL1 and ATF4, respectively. c, Representative images from human melanoma tissue arrays stained for COL1 and ATF4 proteins Scale bars, 100 μm. d, Pearson’s correlation for all the samples (top) and metastatic samples (bottom) between the percentage ATF4 area and percentage COL1 area. e, Kaplan–Meier plot of survival time of patients with SKCM with high (n = 151 biologically independent samples) or low (n = 151 biologically independent samples) COL1A1 expression. log-rank (Mantel–Cox) test.