Autocrine SMO‐dependent signaling: Loss of HHIP or increased HH ligand expression via SOX2‐mediated regulation of hedgehog acetyltransferase HHAT expressiona)Ligand (SMO)‐independent signaling: Direct GLI2 activation by FGFR1 through MAPK signaling (squamous cell lung cancer)Likely non‐canonical SMO‐dependent signaling (cytoskeletal rearrangement in lung cancer cells) Paracrine stromal signaling (lung fibroblasts). The gene discussed is SOX2; the disease is lung cancer.