降低致癌蛋白MCT-1 表現抑制A549 肺腺癌細胞的上皮-間質轉型

The Reduction of MCT-1 Oncoprotein Suppresses Epithelial-Mesenchymal Transition in Invasive A549 Lung Cancer Cells

吳偉祥(Wei-Hsiang Wu)

指導教授 ： 陳令儀 ； 徐欣伶

國立清華大學/生命科學院/分子醫學研究所/碩士(2012年)

https://doi.org/10.6843/NTHU.2012.00027

摘要

致癌蛋白MCT-1 (multiple copies in T-cell malignancy 1) 首先被發現於淋巴癌細胞株，MCT-1基因位於染色體Xq22-24位置，其蛋白由181個胺基酸組成，分子量為20 kDa。MCT-1參與細胞增生、細胞存活和調控蛋白質轉譯功能。近期文獻指出，MCT-1蛋白提升細胞遷移能力並且誘導許多腫瘤轉移及侵襲因子之生成，這暗示著MCT-1蛋白可能參與上皮-間質轉型(Epithelial-Mesenchymal Transition)過程，因此本論文研究目的在探討MCT-1蛋白在EMT中扮演的角色。我們發現在非小細胞肺癌細胞株(A549)降低MCT-1蛋白表現，顯著增加E-cadherin表現量，同時降低vimentin含量。此外，降低MCT-1表現導致ZEB1 (E-cadherin基因轉錄抑制因子)表現量下降，進而增加E-cadherin mRNA表達。再者，降低MCT-1表現可能經由降低EGFR表現去抑制生長因子誘導之EMT。利用傷口癒合、細胞穿透和細胞侵襲能力試驗等證實抑制MCT-1表現之細胞，確實可以明顯抑制細胞遷移能力及侵襲能力。基於上述結果明確顯示：致癌蛋白MCT-1可能發展成為抗腫瘤轉移之標靶，未來我將繼續深入探討其作用機轉及重要相關路徑。

關鍵字

致癌蛋白 MCT-1 ； 上皮-間質轉型 ； 鈣黏蛋白-E ； 轉錄因子 ZEB1 ； 細胞侵襲性 ； 細胞遷移性

並列摘要

The oncoprotein MCT-1 (multiple copies in T-cell malignancy) was identified in a human lymphoma cell line and mapped to chromosome Xq22-24. MCT-1 gene encodes 181 amino acids with molecular mass of 20 kDa. MCT-1 plays an important role in regulating of cell proliferation, cell survival and protein translation. Base on recent studies, oncogenic MCT-1 promotes cell migration and tumorigenic ability, as well as induces a constellation of invasive and metastatic factors. I speculate that MCT-1 is involved in tumor metastatic function. Multiple lines of evidence show that MCT-1 is implicated in the epithelial-mesenchymal transition (EMT) process. The data here demonstrate the up-regulation of E-cadherin and the down-regulation of vimentin proteins in A549 cell are closely associated with MCT-1 silencing. Knockdown of MCT-1 suppresses ZEB1 expression, but enhances E-cadherin gene expression. Moreover, loss of MCT-1 suppresses EMT phenotypes through EGFR signaling pathway. By using wound healing, trans-well and invasion assays, MCT-1 knockdown decreased cell migration and invasion. The mechanism and the potential anti-metastaticity by targeting MCT-1 will be further investigated.

並列關鍵字

MCT-1 ； Epithelial-Mesenchymal Transition ； E-cadherin ； ZEB1 ； cell invasion ； cell migration

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