Zinc-dependent Zip7-MAZ-MYBL2 axis promotes prostate cancer metastasis
Zinc, an essential trace element for healthy prostate, which dramatically decreasesduring prostate tumorigenesis. Targeting the key zinc signaling will be a valuablestrategy for PCa therapy. However, the underlying mechanisms are poorly understood.Here, we show that zinc is significantly decreased in prostate cancer (PCa), especiallyin metastatic PCa. Screening reveals that a zinc transporter Zip7 was upregulated inmetastatic PCa and related to poor progression. Zip7 silencing inhibits PCa cellmigration and invasion in vitro and bone-metastasis in vivo. Mechanistically, weidentify that Zip7 mainly interacts with MAZ in cytoplasm to facilitate MAZ nuclearimport and nuclear MAZ was up-regulated in metastatic prostate cancer tissues andpositively associated with Zip7 expression, which promotes PCa bone metastasis.Furthermore, our RNA-seq studies reveal that Zip7 facilitates MAZ nuclear import topromote MYBL2 transcription. Strikingly, we show in intraarterial injected-bonemetastasis xenograft model that targeting Zip7 by its inhibitor markedly suppressedPCa bone metastasis. Collectively, our findings identify Zip7 is an important regulatorof PCa metastasis and targeting Zinc-dependent Zip7-MAZ-MYBL2 could be avaluable strategy to ameliorate advanced PCa metastasis.