Since both p62 and PTCH1 are NRF2 target genes, and many cancers have been associated with a loss of primary cilia and aberrant Hh signaling, our data reveal a mechanism by which hyperactivation of NRF2, as seen in lung cancer as well as head and neck cancer, promotes tumor progression via dysregulation of a fundamental cellular organelle: the primary cilium and its associated Hh signaling. This evidence concerns the gene SQSTM1 and cancer.