Targeted disruption of the BCL9/beta-catenin complex in colorectal cancer using stapled peptide

我们开发了一种稳定的BCL9螺旋(SAH-BCL9)，它可以靶向β-连环蛋白，解离天然的β-连环蛋白/BCL9复合体，选择性地抑制Wnt转录，并显示出基于机制的抗肿瘤作用。SAH-BCL9还抑制小鼠结直肠癌异种移植模型的肿瘤生长、血管生成、侵袭和转移。SAH-BCL9通过抑制BCL9/β-catenin的相互作用和选择性地抑制癌基因Wnt转录，可能成为Wnt信号失控驱动的癌症的原型治疗剂。

We developed a stabilized a helix of BCL9 (SAH-BCL9), which we show targets beta-catenin, dissociates native beta-catenin/BCL9 complexes, selectively suppresses Wnt transcription, and exhibits mechanism-based antitumor effects. SAH-BCL9also suppresses tumor growth, angiogenesis, invasion, and metastasis in mouse xenograft models of Colo320 colorectal carcinoma. By inhibiting the BCL9/beta-catenin interaction and selectively suppressing oncogenic Wnt transcription, SAH-BCL9 may serve as a prototypetherapeutic agent for cancers driven by deregulated Wnt signaling.