HEY1 and pachyonychia congenita: In PC, several evidences suggest a tumor suppressor role of Notch signaling [33], including its action in promoting PTEN activity [34], the downregulation of Notch1 and HEY1 expression in tumors [34,35], the undetectable levels of Notch1 and ligands in PC cell lines, and the inhibition of PC cell proliferation by ICN [36].