?Np63a mediates sulforaphane suppressed colorectal cancer stem cell properties through transcriptional regulation of Nanog/Oct4/Sox2

Cancer stem cells (CSCs) play a key role in cancer initiation, development, metastasis, and recurrence. Previously, we found that sulforaphane (SFN), a natural compound obtained from cruciferous vegetables, inhibited colorectal CSCs via the downregulation of TAp63 alpha. However, the role of delta Np63 alpha, another critical isoform of p63 which has been considered to contribute to cancer progression, in SFN-mediated colorectal CSCs inhibition remains unclear. Here, we showed that delta Np63 alpha expression was enhanced in sphere-forming colorectal cancer cells. Overexpression of delta Np63 alpha promoted the properties of CSCs, while downregulation of delta Np63 alpha suppressed those properties. Besides, delta Np63 alpha was found to activate the transcription of core CSCs genes including Nanog, Oct4, and Sox2. Furthermore, in vitro and in vivo experiments illustrated the regulatory effects of SFN on delta Np63 alpha and colorectal CSCs. These findings suggested for the first time that delta Np63 alpha activated the transcription of Nanog, Oct4, Sox2 and mediated the interventional effects of SFN on colorectal CSCs, thus providing a novel mechanism by which SFN inhibits colorectal CSCs. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

Cancer stem cells (CSCs) are crucial in cancer and can be targeted by the natural compound SFN through the regulation of delta Np63α expression and the activation of core CSCs gene transcription.