Non-Classical Activation of the Hedgehog Pathway in Human Cancers

Aberrant activation of the Hedgehog (Hh) signaling pathway has been implicated in a number of tumor types, including basal cell carcinoma and medulloblastoma. GLI1 is a target gene and a transcription factor of the Hh signaling pathway in response to binding of the Hh ligand to Patched (PTCH) and activation of Smoothened (SMO).

We have found evidence of cell autonomous activation of GLI1 that is independent of the classic Hh ligand-PTCH-SMO axis in non-small cell lung cancers. Using cultured cell lines, xenograft, and genetic mouse models of lung cancer, we are developing therapeutic strategies to target GLI1 in NSCLC.