Wnt 訊息傳遞路徑與上皮-間質轉化 (EMT) 皆會促使癌幹細胞的重新編程並維持癌幹細胞的特性。然而，對於 Wnt 訊息傳遞路徑與上皮-間質轉化此兩機制對癌幹細胞的影響尚未完全清楚。
高通量染色質免疫沉澱定序 (ChIP-Seq) 指出上皮-間質轉化誘發上皮型態細胞中的 β-catenin/E-cadherin/Sox15 複合體轉換成間質型態細胞中的 β-catenin/Twist1/TCF4 複合體。免疫共沉澱與染色質免疫沉澱實驗更進一步指出：上皮型態細胞中的 β-catenin/E-cadherin/Sox15 複合體可以與 CASP3 基因的近端啟動子區域結合，進而促進 Caspase3 蛋白的表現量；反之， 間質型態細胞中的 β-catenin/Twist1/TCF4 複合體則是活化癌幹細胞相關基因- ABCG2。
接著，我們更詳細的說明：β-catenin/E-cadherin/Sox15複合體中的 E-cadherin 藉由干擾 β-catenin 與 TCF4 的相互結合以降低 β-catenin/TCF4 的轉錄活性，使得細胞核內的 E-cadherin 在 Wnt/β-catenin 訊息傳遞路徑促進癌幹細胞特性的過程中扮演負調控的角色。
在上皮-間質轉化期間，Twist1 藉由提高 β-catenin 的穩定性和TCF4 的入核數量以增強 β-catenin/TCF4 的轉錄活性，進而促進癌幹細胞特性。然而，此正向調控作用卻會因 Caspase3 引起的 Twist1裂解而抵銷。
在臨床應用上，我們利用本論文所建立分子機制中的參與蛋白，為癌幹細胞定義了兩組多基因型標誌 (nuclear E-cadherinLow/nuclear β-cateninHigh/CD133High) (nuclear β-cateninHigh/ nuclear Twist1High/E-cadherinLow/Sox15Low/CD133High)，期望此多基因型癌幹細胞標誌可以為人類肺癌提供一個有用的癌症癒後指標。

Wnt signaling contributes to the reprogramming and maintenance of cancer stem cell (CSC) states that are also activated by epithelial–mesenchymal transition (EMT). However, the mechanistic relationship between EMT and the Wnt pathway in CSC is not entirely clear.
Chromatin immunoprecipitation with highthroughput sequencing (ChIP-seq) indicates that EMT induces a switch from the β-catenin/E-cadherin/Sox15 complex to the β-catenin/Twist1/TCF4 complex. Further tandem coimmunoprecipitation and re-ChIP experiments reveal that the β-catenin/E-cadherin/Sox15 complex in epithelial-type cells binds to the proximal promoter region of CASP3, whereas β-catenin/Twist1/TCF4 complex in mesenchymal-type cells targets to CSC-related gene, ABCG2. In detail, we demonstrate that nuclear E-cadherin, a component of the inhibitory complex, acts as a negative regulator in Wnt/β-catenin-elicited promotion of the CSC phenotype. E-cadherin reduces β-catenin/TCF4 transcriptional activity through abolishing the β-catenin/TCF4 interaction.
During EMT, accumulating Twist1 enhances the transcriptional activity of the β-catenin/TCF4 complex by increasing the stabilization of β-catenin and nuclear translocation of TCF4. Nevertheless, its potent enhancer in the promotion of the CSC phenotype is counteracted by Caspase3-mediated Twist1 cleavage.
In terms of clinical application, our definition of muti-gene CSC signatures (nuclear E-cadherinLow/nuclear β-cateninHigh/CD133High) (nuclear β-cateninHigh/ nuclear Twist1High/E-cadherinLow/Sox15Low/CD133High) may provide a useful prognostic marker for human lung cancer.

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