However, the mechanism of remote mechanotransduction from the bone to the brain and the role of Lrp5-mediated Wnt signaling, which is required for loading-driven bone gain, need to be elucidated.21,22 However, Lrp5 in cancer cells promotes tumor progression, and many challenges have been overcome to block Wnt signaling for cancer treatment.23 Considering the dual role of Wnt signaling in the mechanotransduction of bone and tumor progression, we hypothesized that loading-driven dopamine in the brain downregulates Lrp5 to suppress tumor growth. Here, LRP5 is linked to cancer.