Wnt/β連環蛋白信號肽在癌癥中扮演了關鍵的角色，研究表明β-catenin 在癌癥的引發和發展進程中起到關鍵作用。一個由哈佛大學、斯坦福大學等機構的科研人員在這一方面的研究上取得新突破，相關論文發表在2012年12月13日的Cell雜志上。

Wnt/β-連環蛋白信號途徑在動物生長發育過程中發揮了重要作用。一旦該通路中相關信號傳遞發生異常改變, 就可能導致該通路異常活化, 從而影響生物的胚胎發育、能量代謝等一系列生理過程, 甚至會導致腫瘤的發生及惡化。

YAP（Yes—assoeiatedprotein）即Yes相關蛋白，是一種連接蛋白和轉錄共激活因子，在正常機體細胞內發揮著信號轉導和基因轉錄調節的作用。近年研究發現，YAP是Hippo通路中的靶因子，該通路通過抑制YAP的活性調控細胞增生和凋亡間平衡，抑制組織細胞過度生長。

為破解β-catenin的具體作用機制，研究人員對85種癌細胞中β-catenin的活化進行分類，結果發現了YAP1的調整作用在β-catenin活化癌細胞信號網絡中起到關鍵作用，YAP1和TBX5轉錄因子和β-catenin形成復合體。Yap 1通過酪氨酸激酶YES1磷酸化，結果推動BCL2L1和BIRC5等細胞抗凋亡基因定位。這樣一個小分子抑制劑阻礙擴散癌癥細胞系和動物模型中β- catenin依賴的癌細胞增殖。這些結果表明β- catenin-yap1-tbx5復合體是β- catenin活化癌細胞中起到至關重要的作用。

原文摘要：

β-Catenin-Driven Cancers Require a YAP1 Transcriptional Complex for Survival and Tumorigenesis

Wnt/β-catenin signaling plays a key role in the pathogenesis of colon and other cancers; emerging evidence indicates that oncogenic β-catenin regulates several biological processes essential for cancer initiation and progression. To decipher the role of β-catenin in transformation, we classified β-catenin activity in 85 cancer cell lines in which we performed genome-scale loss-of-function screens and found that β-catenin active cancers are dependent on a signaling pathway involving the transcriptional regulator YAP1. Specifically, we found that YAP1 and the transcription factor TBX5 form a complex with β-catenin. Phosphorylation of YAP1 by the tyrosine kinase YES1 leads to localization of this complex to the promoters of antiapoptotic genes, including BCL2L1 and BIRC5. A small-molecule inhibitor of YES1 impeded the proliferation of β-catenin-dependent cancers in both cell lines and animal models. These observations define a β-catenin-YAP1-TBX5 complex essential to the transformation and survival of β-catenin-driven cancers.