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題 名 | Enhancing Effect of Eps8 on Cervical Cancer Cell Motility by Increasing MMP-9 Expression through ERK1/2 Activation=Eps8經由活化ERK1/2-MMP-9訊息路徑而促進子宮頸癌細胞之移行能力 |
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作 者 | 陳韻如; 蔡秋桃; 洪明權; | 書刊名 | 華醫學報 |
卷 期 | 45 2016.12[民105.12] |
頁 次 | 頁83-109 |
分類號 | 415.138 |
關鍵詞 | 細胞移行能力; Eps8; MMP-9; ERK1/2; Cell motility; |
語 文 | 英文(English) |
中文摘要 | 致癌蛋白 Eps8 已知能促進結腸及乳癌細胞的移行能力。我們這項研究旨在 確定 FAK 和 MMP-9 是否參與在 Eps8 誘導的子宮頸癌細胞移行能力。在控制組 和 Eps8 表現減少的 HeLa 與 SiHa 子宮頸癌細胞上進行的研究顯示,Eps8 的減 弱會降低子宮頸癌細胞的移行能力。Eps8 的減弱不僅減少 FAK Tyr-397 及 Tyr-861 的磷酸化,也降低基質金屬蛋白酶 9(MMP-9)的表現。而將 Eps 送回表 現減低之 HeLa 細胞則可使上述這些因 Eps8 減弱所產生的變化有一定程度的 回復,顯示 eps8 siRNA 的作用是具有專一性的。在以 PD98059 處理子宮頸癌 細胞上發現細胞的移行能力,ERK 的活化和 MMP 9 的表現會同時被抑制,顯 示 Eps8 所媒介的 MMP-9 蛋白的表達是有 ERK 依賴性的。的確,basal ERK 活 性在 EPS8 減弱的 HeLa 與 SiHa 子宮頸癌細胞有降低的情形,而這現象可通過 EPS8 的還原表達來回復。MMP-9 專一性抑製劑可以在不影響 ERK1 / 2 的活性 下而減少 HeLa 及其所衍生之細胞的移行能力,顯示 MMP-9 的表達的確在 ERK1 / 2 的下游。綜合以上結果,我們在子宮頸癌細胞中確立了 Eps8 可經由活化 ERK 而促進 MMP-9 的表現;同時,此條訊息傳遞路徑參與在部份 Eps8 所調控的子 宮頸癌細胞移行能力中。這項發現拓寬了我們對 Eps8 媒介的細胞移行過程的理 解。 |
英文摘要 | The oncoprotein Eps8 is known to facilitate colon and breast cancer cell motility. Our present study sought to determine whether FAK and MMP-9 were involved in Eps8-induced cervical cancer cell motility. Studies conducted in control and Eps8-attenuated HeLa and SiHa cervical cancer cells revealed that cell mobility was reduced in both Eps8-attenuated HeLa and SiHa cells. Diminished Eps8 not only led to reduced FAK Pi-Tyr-397 and Pi-Tyr-861, but also the expression of matrix metalloproteinase 9 (MMP-9). Restored expression of Eps8 in HeLa cells with eps8 siRNA reversed all the biological events just mentioned. The simultaneous inhibition of cell motility, ERK activation and MMP9 expression in cells treated with PD98059 implicated the involvement of Eps8 in MMP9 enhancement, which was ERK-dependent. Indeed, suppressed ERK activation was observed in Eps8-attenuated cells, which could be recovered by the restored expression of Eps8. MMP-9 specific inhibitor could decrease motility in HeLa and its derived cells without affecting ERK1/2 activity, indicating that MMP-9 expression was indeed downstream of ERK1/2. Taken together, our results demonstrate that, in addition to FAK, Eps8 can regulate the expression of MMP-9 by virtue of ERK activation. This novel finding broadens our understanding towards Eps8-mediated cell migratory process. |
本系統中英文摘要資訊取自各篇刊載內容。