The Role of Smoothened in Cancer

Int J Mol Sci. 2020 Sep 18;21(18):6863. doi: 10.3390/ijms21186863.


Smoothened (SMO) belongs to the Hedgehog (HH) signaling pathway, which regulates cell growth, migration, invasion and stem cells in cancer. The HH signaling pathway includes both canonical and noncanonical pathways. The canonical HH pathway functions through major HH molecules such as HH ligands, PTCH, SMO and GLI, whereas the noncanonical HH pathway involves the activation of SMO or GLI through other pathways. The role of SMO has been discussed in different types of cancer, including breast, liver, pancreatic and colon cancers. SMO expression correlates with tumor size, invasiveness, metastasis and recurrence. In addition, SMO inhibitors can suppress cancer formation, reduce the proliferation of cancer cells, trigger apoptosis and suppress cancer stem cell activity. A better understanding of the role of SMO in cancer could contribute to the development of novel therapeutic approaches.

Keywords: Hedgehog signaling pathway; Smoothened; cancer stem cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism*
  • Female
  • Hedgehog Proteins / metabolism
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism*
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Smoothened Receptor / antagonists & inhibitors*
  • Smoothened Receptor / metabolism


  • Antineoplastic Agents
  • Hedgehog Proteins
  • Smoothened Receptor