Altogether, our findings, summarized in Figure 7, point to (1) a shift in ANXA2 expression when comparing primary prostate tumors with bone metastatic PCa; (2) paracrine factors released from both the tumor and bone niche impacting on ANXA2 expression and signaling, favoring in this way the colonization and progression of the tumor cells in the skeletal metastatic site, and (3) HO-1 modulation in tumor cells, clearly interfering with this signaling. Here, HMOX1 is linked to posterior cortical atrophy.