FIGURE 1.

Emergence of STAT1 in advanced PCa contributes to the acquisition of self‐renewal capacity in PCSCs. (A,B) GSEA identifying upregulation of genes associated with IFNα and IFNγ response in the tumour specimens of PCa patients with lymph node metastasis (N1, Red, n = 80), compared to cohort without metastasis (N0, Blue, n = 345). (C) TCGA PCa dataset demonstrating STAT1 expression level among stage T2 (n = 187), T3 (n = 293) and T4 (n = 11) PCa patients. (D) TCGA PCa dataset demonstrating elevation of STAT1 in PCa patients with lymph node metastasis (N1, n = 80), compared to cohort without metastasis (N0, n = 345). (E) Clinical correlation of STAT1 with interferon response‐associated genes (N = 550) derived from TCGA PCa dataset was calculated using Pearson Correlation. (F) Expression level of interferon response‐associated genes in PCa patients with lymph node metastasis (N1, n = 80), compared to cohort without metastasis (N0, n = 345). (G) The sphere forming ability of sgTP53/RB1‐LNCaP cell, compared to vector control (sgNT). (H) Protein level of STAT1, RB1 and TP53 in sgTP53/RB1‐LNCaP cell, compared to vector control (sgNT). (I) Left: morphology of DU145, 22Rv1 and C4‐2 cells under adherent monolayer or ultra‐low attachment sphere culture condition. Right: JAK1 and STAT1 protein expression in the sphere (S) derived from each PCa line, compared to corresponding monolayer (M) culture. (J) Heat map illustrating the expression profile of JAK‐STAT signalling pathway molecules in the sphere (S) derived from LNCaP cells, compared to monolayer (M) adherent culture. (K,L) Dose‐dependent impact of fludarabine and ruxolitinib on the sphere forming ability of sgTP53/RB1‐LNCaP cells. Cells were treated with either fludarabine or ruxolitinib at corresponding concentration right after seeding into the ultra‐low attachment plate. Quantitation of sphere forming ability is done at 2 weeks afterward. (ns = no significant differences, *p < .05, **p < .001, ***p < .0001)