By genetic silencing of ALDH1A1 and ALDH1A3 in vitro in xenografted zebrafish and murine models, and by comparative immunohistochemical analyses of benign, primary tumor, and metastatic specimens from patients with PCa, we demonstrated that ALDH1A1 and ALDH1A3 maintain the CSC phenotype and radioresistance and regulate bone metastasis-initiating cells. Here, ALDH1A1 is linked to posterior cortical atrophy.