Figure 7.

FOXC2 knockdown blocks migration and plasticity phenotype and FOXC2 expression significantly correlates with insulin receptor expression in PCa patient samples. (A) LNCaP cells with constitutive FOXC2 knockdown did not migrate through transwell in response to insulin treatment, unlike their control counterparts with scramble knockdown (Scale bars = 100 μm). (B) LNCaP cells with constitutive FOXC2 knockdown were also unable to up-regulate several EMT and NE markers in response to insulin (Ins) treatment compared to vehicle (Veh), unlike FF3 control cells. Knockdown of FOXC2 prevented insulin induced rise in Zeb1. Linear regression shows a significant positive association between FOXC2 and INSR in PCa patients with localized and mCRPC tumors in both (C) Grasso and (D) Yu datasets. (E) Kaplan-Meier survival curve shows FOXC2 expression is significantly associated with overall survival in mCRPC patients with wild type AR amplification mutation in Grasso. Median overall survival is significantly reduced by 62% in patients with metastatic tumors expressing high levels of FOXC2 compared with patients with low level of FOXC2 expression (F) Box-plots showing FOXC2 mRNA is significantly increased in the metastatic PCa tumors (M) (patient numbers in brackets) compared to primary tumors (P) in three datasets, accessed using Oncomine^TM (*p < 0.05, **p < 0.01, One-way ANOVA, ±SEM with vehicle as control).