Nuclear receptors as molecular regulator and chemopreventive targets of colon cancer stem cells.

越来越多的证据表明，结肠癌干细胞(CCSC)与肿瘤的发生、发展和复发有关。为了在CCSC中建立与结肠癌的发生和发展有关的信号通路，我们从已建立的细胞系中检测了CCSC中富含CCSC的结肠球中的核受体信号。我们发现，结肠癌细胞系形成的结肠球高度富含CCSC，Wnt/b-catenin途径在结肠球的生长和维持中起着关键作用。我们还发现，呋喃西丁醇和1a，25-二羟基维生素D3通过下调PPARg和NFkB p52对CCSC细胞的生长起作用，并作为预防结肠癌的内在因素。这些发现确立了PPARg和维生素D受体(VDR)在结肠癌细胞生长调节中的关键作用，这些作用是通过这些核信号通路之间的功能相关的串扰实现的。

Increasing evidence suggests that colon cancer stem cells (CCSC) have responsible for carcinogenesis, cancer development and recurrence. To establish signaling pathways in CCSC, which are implicated in the initiation and progression of colon cancer, we examined nuclear receptor signaling in colonospheres that are enriched in CCSC from established cell lines. We found that colonospheres formed by colon cancer cell lines are highly enriched in CCSC and that Wnt/b-catenin pathway plays a critical role in growth and maintenance of colonospheres. We also found that the combination of Fucoxanthinol and 1a,25-dihydroxyvitamin D3 acts on the CCSC cell growth through down-regulation of PPARg and NFkB p52, and as an intrinsic factor for the prevention of colon cancer. These findings establish a critical role for PPARg and vitamin D receptor (VDR) in growth regulation in colon cancer cells via functionally relevant cross-talk between these nuclear signaling pathways.