| 結束日期 |
2012-03-31 |
| 計畫單位 |
醫學院癌症生物學研究所;中國附醫分子醫學中心生物醫學 |
| 計畫主持人 |
蘇振良(Jen-Liang Su) |
| 摘要 |
Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the Mesenchymal-Epithelial Transition (MET) in lung cancer cells. We found that resveratrol-mediated downregulation of FOXC2 (forkhead box C2) is critical for the suppression of tumor metastasis in in vitro and in vivo models. Furthermore, we identified that expression of protein phosphatase 2A/C (PP2A/C) is enhanced by resveratrol, which accelerated Akt dephosphorylation and NFκB inactivation, whereas mutation of NFκB binding site on FOXC2 promoter completely mitigated the resveratrol-suppressed FOXC2 expression. In addition to the downregulation of PP2A/C and upregulation of FOXC2 in patients with poor prognosis, we identified an inverse correlation between PP2A/C and FOXC2 in lung cancer tissues. Together, we demonstrate, for the first time, the underlying mechanism namely, resveratrol → PP2A/C Akt → NFκB → FOXC2→ EMT→ metastasis, in which resveratrol inhibited lung cancer metastasis through enhancing PP2A/C-mediated suppression on NFκB-induced FOXC2 expression. |
| 關鍵字 |
FOXC2, resveratrol, metastasis, PP2A/C |
| 相關附件 |
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