摘要：SummaryTransforming growth factor β (TGF-β) enhances migration and invasion of cancer cells, causing life-threatening metastasis. Smad7 expression is induced by TGF-β to control TGF-β signaling in a negative feedback manner. Here we report an additional function of Smad7, i.e., to enhance TGF-β induction ofc-JunandHDAC6via binding to their regulatory regions, promoting migration and invasion of prostate cancer cells. Lysine 102 in Smad7 is crucial for binding to specific consensus sites inc-JunandHDAC6,even when endogenous Smad2, 3, and 4 were silenced by siRNA. A correlation between the mRNA expression ofSmad7andHDAC6,Smad7andc-Jun, andc-JunandHDAC6was found in public databases from analyses of prostate cancer tissues. High expression of Smad7, HDAC6, and c-Jun correlated with poor prognosis for patients with prostate cancer. The knowledge that Smad7 can activate transcription of proinvasive genes leading to prostate cancer progression provides clinically relevant information.Graphical AbstractDisplay OmittedHighlights•TGF-β promotes prostate cancer cell migration and invasion, via Smad7•Lysine 102 in Smad7 binds to DNA in regulatory regions ofHDAC6andc-Jun•Smad7 regulates expression of HDAC6 and c-Jun in prostate cancer in response to TGF-β•High levels of Smad7, c-Jun, and HDAC6 are found in aggressive prostate cancer tissuesMolecular Biology; Cell Biology; Cancer
