Since tumor initiating cells (TICs) were linked to the chemo-resistance [21, 22], and sphere formation was used to identify the TICs characteristic of self-renewal in vitro, we also knocked down TR4 in PCa cells and results revealed suppressing TR4 reduced sphere formation in C4-2-R and 22RV-1-R cells (Fig. 2f, g), indicating targeting TR4 may reduce the TICs and chemo-resistance in the DTX-resistant PCa cells. This evidence concerns the gene NR2C2 and posterior cortical atrophy.