Molecular mechanisms of suppressor of fused in regulating the hedgehog signalling pathway

Highly conserved throughout evolution, the hedgehog (Hh) signalling pathway has been demonstrated to be involved in embryonic development, stem cell maintenance and tissue homeostasis in animals ranging from invertebrates to vertebrates. In the human body, a variety of cancer types are associated with the aberrantly activated Hh signalling pathway. Multiple studies have revealed suppressor of fused (Sufu) as a key negative regulator of this signalling pathway. In vertebrates, Sufu primarily functions as a tumor suppressor factor by interacting with and inhibiting glioma-associated oncogene homologues (GLIs), which are the terminal transcription factors of the Hh signalling pathway and belong to the Kruppel family of zinc finger proteins; by contrast, the regulation of Sufu itself remains relatively unclear. In the present review article, we focus on the effects of Sufu on the Hh signalling pathway in tumourigenesis and the molecular mechanisms underlying the regulation of GLI by Sufu. In addition, the factors modulating the activity of Sufu at post-transcriptional levels are also discussed.