Cancer stem cells (CSCs) have an established role in cancer progression and therapeutic resistance. The p63 proteins are important transcription factors which belong to the p53 family, but their function and mechanism in CSCs remain elusive. Here, we investigated the role of TAp63α in colorectal CSCs and the effects of sulforaphane on TAp63α. We found that TAp63α was upregulated in spheres with stem cell properties compared to the parental cells. Overexpression of TAp63α promoted self-renewal capacity and enhanced CSC markers expression in colorectal sphere-forming cells. Furthermore, we showed that TAp63α directly bound to the promoter region of Lgr5 to enhance its expression and activate its downstream β-catenin pathway. Functional experiments revealed that sulforaphane suppressed the stemness of colorectal CSCs both in vitro and in vivo. Upregulation of TAp63α attenuated the inhibitory effect of sulforaphane on colorectal CSCs, indicating the role of TAp63α in sulforaphane suppression of the stemness in colorectal cancer. The present study elucidated for the first time that TAp63α promoted CSCs through targeting Lgr5/β-catenin axis and participated in sulforaphane inhibition of the stem cell properties in colorectal cancer.

癌症干细胞 (CSCs) 在癌症进展和治疗抵抗中发挥着既定的作用。p63 蛋白是重要的转录因子，属于 p53 家族，但它们在 CSC 中的功能和机制仍然难以捉摸。在这里，我们研究了 TAp63α 在结直肠 CSC 中的作用以及萝卜硫素对 TAp63α 的影响。我们发现与亲本细胞相比，TAp63α 在具有干细胞特性的球体中上调。TAp63α 的过表达促进了结直肠球形成细胞中的自我更新能力并增强了 CSC 标志物的表达。此外，我们发现 TAp63α 直接与 Lgr5 的启动子区域结合以增强其表达并激活其下游 β-连环蛋白途径。功能实验表明，萝卜硫素在体外和体内均可抑制结直肠 CSC 的干性。TAp63α 的上调减弱了萝卜硫素对结直肠癌干细胞的抑制作用，表明 TAp63α 在萝卜硫素抑制结直肠癌干细胞中的作用。本研究首次阐明TAp63α通过靶向Lgr5/β-catenin轴促进CSCs并参与萝卜硫素对结直肠癌干细胞特性的抑制。