Fig. 6: GFAT1-TAB1-TTLL5 axis promotes tumorigenesis and is related to poor prognosis.
a Expression of rTAB1-S438A or rTAB1-E212A suppressed tumorigenesis. A total of 5 × 106 A549 cells with TAB1 depletion and reconstituted expression of the WT rTAB1, rTAB1-S438A or rTAB1-E212A were subcutaneously injected into athymic nude mice. Representative tumour xenografts are shown (upper panel). Tumor volumes were measured by using length “a” and width “b” and calculated using the following equation: V = ab2/2. b Expression of rTAB1-S438A or rTAB1-E212A suppressed TAB1-p38-autophagy axis. Immunoprecipitated HA-rTAB1 from lysates of A549 cells that were cultured for 8 h under glucose deprivation and 7 pooled tumor tissues (as indicated in a) was subjected to immunoblotting analyses using the indicated antibodies. c Immunohistochemical staining was performed on 87 human lung adenocarcinoma specimens using the indicated antibodies. Representative images are shown. Scale bars, 50 µm. d Semi-quantitative scoring and correlation analysis indicating the correlation between p-p38 and TAB1 pSer438 (Person correlation test; r = 0.536, P < 0.001). e The survival durations for 87 patients with low (0–2 staining scores, blue curve) versus high (3–6 staining scores, red curve) GFAT1 (low, n = 27 patients; high, n = 60 patients) and with low (0–2 staining scores, blue curve) versus high (3–6 staining scores, red curve) TAB1 Ser438 phosphorylation (low, n = 30 patients; high, n = 57 patients) were compared. The Kaplan–Meier method and log-rank tests indicate the significance level of the association of GFAT1 (P = 0.0379) with patient survival and the significance level of the association of TAB1 Ser438 phosphorylation (P = 0.0138) with patient survival. The table shows the Cox multivariate analysis after adjustment for patient sex and age, indicating the significance level of the association of GFAT1 (P = 0.043, HR = 1.925) with patient survival and the significance level of the association of TAB1 Ser438 phosphorylation (P = 0.017, HR = 2.205) with patient survival. In a, the values are presented as means ± SEM, n = 7; ***P < 0.001, Student’s t-test, two-sided.
