Figure 5. Significantly activated ERBB2... | Rockefeller University Press

Figure 5.

Significantly activated ERBB2 (HER2) signaling pathway in invasive fibroblasts. (A and B) Dot plot visualization of the −Log10(FDR) (A) and bar plot visualization of the activation Z-score (B) of the top 30 activated and inhibited upstream regulators of invasive fibroblasts by IPA analysis. ERBB2 was the most activated regulators of invasive fibroblasts. ERBB2 was highlighted as the most activated regulator. (C) IPA analysis revealed the upstream regulators of metastatic lung adenocarcinoma cancer cells compared to primary cancer cells retrieved from GSE131907. Most of the top activated/inhibited (listed in red/green texts, respectively) upstream regulators of invasive fibroblasts were these of metastatic cancer cells. (D) Pearson correlation analysis of activation z-score of shared upstream regulators (n = 129) of invasive fibroblasts versus metastatic lung adenocarcinoma cancer cell. Linear regression analysis was performed and visualized in red line. (E) p-HER2, total HER2, and SEMA7A protein levels in sorted SEMA7A high and negative fibroblasts in nine IPF fibroblast lines were determined by Western blot. GAPDH served as loading control. (F) Quantification of the Western blot was used to determine the relative protein levels of p-HER2, total HER2, and SEMA7A in E (n = 9 per group). (G and H) p-HER2 and total HER2 in sorted fibroblasts from three normal and four IPF lung were determined by Western blot and quantification was performed (H; n = 4). Neg, megative; P, proximal lung regions; D, distal lung regions. Two independent experiments were performed on fibroblasts from different patients (F and H). Data are the mean ± SEM. *, P < 0.05; **, P < 0.01; ****, P < 0.0001 by Student’s t test (F and H). Source data are available for this figure: SourceData F5.

Significantly activated ERBB2 (HER2) signaling pathway in invasive fibroblasts. (A and B) Dot plot visualization of the −Log₁₀(FDR) (A) and bar plot visualization of the activation Z-score (B) of the top 30 activated and inhibited upstream regulators of invasive fibroblasts by IPA analysis. ERBB2 was the most activated regulators of invasive fibroblasts. ERBB2 was highlighted as the most activated regulator. (C) IPA analysis revealed the upstream regulators of metastatic lung adenocarcinoma cancer cells compared to primary cancer cells retrieved from GSE131907. Most of the top activated/inhibited (listed in red/green texts, respectively) upstream regulators of invasive fibroblasts were these of metastatic cancer cells. (D) Pearson correlation analysis of activation z-score of shared upstream regulators (n = 129) of invasive fibroblasts versus metastatic lung adenocarcinoma cancer cell. Linear regression analysis was performed and visualized in red line. (E) p-HER2, total HER2, and SEMA7A protein levels in sorted SEMA7A high and negative fibroblasts in nine IPF fibroblast lines were determined by Western blot. GAPDH served as loading control. (F) Quantification of the Western blot was used to determine the relative protein levels of p-HER2, total HER2, and SEMA7A in E (n = 9 per group). (G and H) p-HER2 and total HER2 in sorted fibroblasts from three normal and four IPF lung were determined by Western blot and quantification was performed (H; n = 4). Neg, megative; P, proximal lung regions; D, distal lung regions. Two independent experiments were performed on fibroblasts from different patients (F and H). Data are the mean ± SEM. *, P < 0.05; **, P < 0.01; ****, P < 0.0001 by Student’s t test (F and H). Source data are available for this figure: SourceData F5.