p63 sustains self-renewal of mammary cancer stem cells through regulation of Sonic Hedgehog signaling
Abstract
p63, the sister homolog of p53, is a master regulator of epithelial stem cell (SC) biology. p63 is indeed intimately implicated in the maintenance of the self-renewal capacity of stratified epithelia and their derivatives, including the mammary gland. Although the physiological role of p63 in normal mammary SCs is now acknowledged, proof of its implications in breast cancer SCs remains elusive. Here, we find that mammary cancer stem cells (CSCs) possess increased levels of p63 expression compared with normal progenitors. p63 promotes self-renewal and expansion of mammary CSCs and breast tumor growth in vivo. Additionally, this study provides a link between p63 and the Sonic Hedgehog signaling pathway in the regulation of breast cancer stemness.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- March 2015
- DOI:
- 10.1073/pnas.1500762112
- Bibcode:
- 2015PNAS..112.3499M