Supplementary data related to Fig. 3. (A) Western blotting of either nontargeting cET-ASO^NT or cET-ASO^Kras–treated KPC cells, showing the absence of phosphorylation induction on EPHA2 Tyr⁵⁸⁸ and AKT Ser⁴⁷³. GAPDH was used as a loading control. (B) Western blotting of either nontargeting cET-ASO^NT or cET-ASO^Kras–treated KPC cells, showing the induction of phosphorylation on JNK Tyr¹⁸⁵ and Thr²²¹, MEK1/2 Ser²¹⁷ and Ser²²¹, as well as the lack of induction of phosphorylation on p38MAPK Thr¹⁸⁰ and Tyr¹⁸². Vinculin was used as a loading control. (C) Western blotting in either cET-ASO^NT or cET-ASO^Kras–treated KPC cells, showing the induction of phosphorylation on JNK Tyr¹⁸⁵ and Thr²²¹ and the lack of induction of phosphorylation on AKT Ser⁴⁷³ in KPC Epha2^−/− cells. Western blotting was performed on the same samples that were used for the experiment presented in Fig. 3 D. Thus, the vinculin blot used as a loading control in Fig. 3 D is also used as a sample control in this panel. (D) Western blotting showing the induction of the phosphorylation of EPHA2 Ser⁸⁹⁷, p90RSK Ser³⁸⁰, and ERK1/2 Tyr^202/204 in cET-ASO^Kras–treated EPHA2^+/+ and EPHA2^CRISPR-KO H1299 cells. * Band corresponds to the band previously obtained by blotting for EPHA2 phospho-Ser⁸⁹⁷. Histone H3 was used as a loading control. (E) Heatmap showing levels of mRNA expression (RNA-seq normalized reads) of each member of the SR family in either EPHA2^+/+ (top) or EPHA2-siRNA depleted (bottom) H1299 cells. Red text corresponds to the highest expressed genes both in KPC and H1299 cells. Outlier values are indicated in dark brown. (F) PDAC patient tumor tissue immunostaining. Top panels show the staining of EPHA2 (green) and SCARB1 (red) within the tumor nodules. Bottom panels correspond to amplification of the area contained in the white dotted line frame. (G) PDAC patient tumor tissue immunostaining. Top panels show the staining of EPHA2 (green) and SR-K1 (CD44, red) within the tumor nodules. Bottom panels correspond to amplification of the area contained in the white dotted line frame. (H)Scarb1 and Cd44 mRNA expression levels in KPC cells transduced with either a nontargeting sgRNA (n.t.) or four different sgRNAs targeting either Scarb1 (Scarb1^CRISPR-KO) or Cd44 (Cd44^CRISPR-KO). Dots represent n = 3 independent experiments. (I) Western blotting showing the protein expression of either SCARB1 in nontargeting and Scarb1^CRISPR-KO KPC cells, or CD44 in Cd44^CRISPR-KO KPC cells. GAPDH is a loading control. (J)Kras mRNA expression in either nontargeting or Scarb1^CRISPR-KO KPC cell lines treated with either 0.5 μM or 1 μM cET-ASO^Kras for 72 h. Two-way ANOVA, Dunnett multiple comparison test, n = 5 independent experiments. (K) Western blotting showing the effect of Scarb1 depletion in Scarb1^CRISPR-KO KPC cell lines on the cET-ASO^Kras–induced activation of ERK1/2 Tyr^202/204, p90RSK Ser³⁸⁰, and EPHA2 Ser⁸⁹⁷ phosphorylation. GAPDH was used as a loading control. (L)SCARB1 and CD44 mRNA expression in H1299 cells transduced with either a nontargeting siRNA or a pooled siRNA for each respective scavenging receptor. Results expressed as the fold change of each mRNA in nontargeting transduced cells, n = 3 independent experiments. (M)KRAS mRNA expression in H1299 cells transduced with either a nontargeting siRNA or a pooled siRNA for each respective scavenging receptor, treated with either 0.5 μM or 1 µM cET-ASO^Kras for 72 h. Two-way ANOVA, Tukey multiple comparison test, n = 3 independent experiments. (N) Western blotting showing the effect of depletion of SCARB1 and CD44 SRs in H1299 cell lines on the MAPK signalling activation and KRAS expression after 72 h of cET-ASO^Kras addition. β-tubulin was used as a loading control. Source data are available for this figure: SourceData FS2.