Research ArticleCancer

The protein kinase p38α destabilizes p63 to limit epidermal stem cell frequency and tumorigenic potential

See allHide authors and affiliations

Science Signaling  09 Oct 2018:
Vol. 11, Issue 551, eaau0727
DOI: 10.1126/scisignal.aau0727

A p38α-p63 balancing act in skin cancer

Loss of p38α in mice leads to hyperplasia and tumor development in epithelial tissues. Choo et al. analyzed skin tissue and cells from normal donors, patients with premalignant keratosis or squamous cell carcinoma (SCC), and mouse models and found that p38α phosphorylated and consequently induced the degradation of the transcription factor p63, particularly that of its tumor-associated isoform ΔNp63α. Loss of p38α increased p63 abundance in the skin and thereby enhanced the expression of stem cell–associated genes, repressed the expression of a tumor-suppressive metalloprotease, and promoted stem cell outgrowth in the skin. The findings also raise the possibility that p38α inhibitors used to treat other cancers (where p38α is tumor promotive) may cause secondary SCC in patients.

View Full Text

Stay Connected to Science Signaling