在現今工業發達的時代中，人們常可以於環境中暴露至許多的多環芳香烴 (PAHs)，而這些多環芳香烴物質主要是透過多環芳香烴受體 (AhR)進行活化代 謝反應。然而在肺癌病人身上，癌細胞本身所帶有的 AhR，對於末期肺癌病人 常會發生癌症轉移的現象之間的研究需求性便十分急迫。故本實驗透過 H1299 以及 CL1-0 兩不同肺癌細胞株，將其細胞內的 AhR 大量表現後，探討與 EMT 間的關係，結果也顯示，大量表現 AhR 的細胞中，能夠誘使 Jab1 蛋白與 smad4 蛋白間的交互作用增加，並且將 ubiquitin 接上 smad4 後使其被 26S 蛋白酶體 (proteasome)辨認，驅使 smad4 受到降解 (degradation)，此一現象造成 smad4 含 量低下後無法輔助受到 TGF-β/BMP 刺激活化的 R-samd 共同進入至細胞核當中 進行轉錄工作，而 TGF-β/BMP pathway 的轉錄工作受到抑制後，原先受到其誘 導的 EMT 相關轉錄因子 snail、ID1 此時便無法被生合成，缺乏 EMT 轉錄因子 後，持續惡化的癌細胞，便無法透過改變上皮與間質性指標進而促成 EMT 作 用，最後便會因為上皮細胞無法轉換成為高度移行的間質細胞，而達到抑制癌 細胞轉移的目的，本研究希望能透過未受到配體活化的 AhR 蛋白層面做為探 討，提供一個 AhR 抑制癌症轉移的治療方針 (Figure 7)。
46
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