بيانات النشر: Uppsala universitet, Science for Life Laboratory, SciLifeLab
Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi
Uppsala Univ, Ludwig Inst Canc Res Ltd
Umeå Univ, Dept Med Biosci, S-90187 Umeå, Sweden.
Showa Pharmaceut Univ, Lab Biochem, Tokyo 1948543, Japan.
Uppsala Univ, Ludwig Inst Canc Res Ltd;Umeå Univ, Dept Med Biosci, S-90187 Umeå, Sweden.
CELL PRESS
نبذة مختصرة : Transforming growth factor beta (TGF-beta) enhances migration and invasion of cancer cells, causing life-threatening metastasis. Smad7 expression is induced by TGF-beta to control TGF-beta signaling in a negative feedback manner. Here we report an additional function of Smad7, i.e., to enhance TGF-beta induction of c-Jun and HDAC6 via 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 in c-Jun and HDAC6, even when endogenous Smad2, 3, and 4 were silenced by siRNA. A correlation between the mRNA expression of Smad7 and HDAC6, Smad7 and c-Jun, and c-Jun and HDAC6 was 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.
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