Hedgehog/GLI-E2F1-iASPP: a novel axis involved in melanoma cell growth

The Hedgehog-GLI (HH-GLI) signaling is a conserved pathway, which plays an important role in regulating tissue development; its aberrant activation is involved in several tumor types, including melanoma. In this study we show that the transcription factor E2F1 is a direct target of HH pathway in melanoma cells. Functionally, we evaluated the role of E2F1 in mediating the effects of HH pathway activation in melanoma. Moreover, we present evidence that the HH/GLI-E2F1 axis positively regulates iASPP (inhibitor of apoptosis-stimulating protein p53) expression and function in melanoma cells. These findings suggest the presence of a novel HH/GLI-E2F1-iASPP axis involved in melanoma cell growth regulation, and provides an additional mechanism through which activation of HH signaling restrains p53 proapoptotic function.