Fig. 7: NURR1 can function to enhance in vivo metastasis potential of prostate cancer cells as assayed using a zebrafish embryo model.

A Picture illustrates the microinjection of RFP-labeled PC-3-NURR1/vector infectants into the developing heart of flk:GFP zebrafish fry (48-h post fertilization). B Fluorescent microscopic images of migrated PC-3-NURR1/vector infectants detected in cranial (head) and caudal (tail) regions of zebrafish at 4-day post-injections. Green: blood vessels; red: PC-3 infectants. Microscopic examination showed that at 4-day post injections, significant number of PC-3-NURR1 infectants were detected in both head and tail regions of zebrafish, whereas almost absence of PC-3-vector infectants were detected in these regions. However, significant number of PC-3-vector infectants were detected in zebrafish upon treatment with C-DIM-12. On the other hand, no PC-3-NURR1 infectants with CTNNB1 knockout were detected in cranial and caudal regions of zebrafish but with few cells detected in the blood vessels. C Quantification analysis of PC-3-NURR1/vector infectants migrated to head and tail regions of zebrafish. D RT-qPCR analysis of EMT markers expressed in PC-3-NURR1/vector infectants as migrated to distal sites of zebrafish. Results showed that the migrated PC-3-NURR1 infectants exhibited enhanced expression profiles of EMT markers (increased SNAIL1 and KLF4 levels and decreased E-cadherin level) as compared to that in PC-3-vector infectants. Treatment of zebrafish with C-DIM-12 could significantly increase CD44 expression. Migrated PC-3-NURR1 infectants with CTNNB1 knockout showed reduced MMP9 expression. *P < 0.05; **P < 0.01; ***P < 0.001 versus vector or scramble controls. E Schematic diagram depicts the characterized role of NURR1 in the promotion of castration-resistance, metastasis and cancer stemness in advanced prostate cancer via its direct targeting of CTNNB1 (β-catenin).