The role of the Hedgehog signaling pathway in cancer: A comprehensive review


  • Ana Marija Skoda Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia
  • Dora Simovic Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia
  • Valentina Karin Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia
  • Vedran Kardum Department of Obstetrics and Gynecology, University Hospital Merkur, Zagreb Croatia
  • Semir Vranic College of Medicine, Qatar University, Doha, Qatar
  • Ljiljana Serman Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia



Hedgehog signaling pathway, Hh, tumorigenesis, signal transduction


The Hedgehog (Hh) signaling pathway was first identified in the common fruit fly. It is a highly conserved evolutionary pathway of signal transmission from the cell membrane to the nucleus. The Hh signaling pathway plays an important role in the embryonic development. It exerts its biological effects through a signaling cascade that culminates in a change of balance between activator and repressor forms of glioma-associated oncogene (Gli) transcription factors. The components of the Hh signaling pathway involved in the signaling transfer to the Gli transcription factors include Hedgehog ligands (Sonic Hh [SHh], Indian Hh [IHh], and Desert Hh [DHh]), Patched receptor (Ptch1, Ptch2), Smoothened receptor (Smo), Suppressor of fused homolog (Sufu), kinesin protein Kif7, protein kinase A (PKA), and cyclic adenosine monophosphate (cAMP). The activator form of Gli travels to the nucleus and stimulates the transcription of the target genes by binding to their promoters. The main target genes of the Hh signaling pathway are PTCH1, PTCH2, and GLI1. Deregulation of the Hh signaling pathway is associated with developmental anomalies and cancer, including Gorlin syndrome, and sporadic cancers, such as basal cell carcinoma, medulloblastoma, pancreatic, breast, colon, ovarian, and small-cell lung carcinomas. The aberrant activation of the Hh signaling pathway is caused by mutations in the related genes (ligand-independent signaling) or by the excessive expression of the Hh signaling molecules (ligand-dependent signaling – autocrine or paracrine). Several Hh signaling pathway inhibitors, such as vismodegib and sonidegib, have been developed for cancer treatment. These drugs are regarded as promising cancer therapies, especially for patients with refractory/advanced cancers.


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Author Biographies

  • Ana Marija Skoda, Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia
    Department of Biology
  • Dora Simovic, Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia
    Department of Biology
  • Valentina Karin, Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia
    Department of Biology
  • Vedran Kardum, Department of Obstetrics and Gynecology, University Hospital Merkur, Zagreb Croatia
    Department of Obstetrics and Gynecology
  • Ljiljana Serman, Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia
    Department of Biology


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The role of the Hedgehog signaling pathway in cancer: A comprehensive review


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The role of the Hedgehog signaling pathway in cancer: A comprehensive review. Biomol Biomed [Internet]. 2018 Feb. 20 [cited 2024 May 19];18(1):8-20. Available from: