smoothened receptor


Summary: A frizzled-like, G-protein-coupled receptor that associates with PATCHED RECEPTORS to transduce signals from HEDGEHOG PROTEINS and initiate hedgehog signaling to ZINC FINGER PROTEIN GLI1. It may normally inhibit signaling in the absence of SONIC HEDGEHOG PROTEIN binding to PATCHED RECEPTOR-1.

Top Publications

  1. Snouffer A, Brown D, Lee H, Walsh J, Lupu F, Norman R, et al. Cell Cycle-Related Kinase (CCRK) regulates ciliogenesis and Hedgehog signaling in mice. PLoS Genet. 2017;13:e1006912 pubmed publisher
  2. Lin Y, Huang Y, He J, Chen F, He Y, Zhang W. Role of Hedgehog-Gli1 signaling in the enhanced proliferation and differentiation of MG63 cells enabled by hierarchical micro-/nanotextured topography. Int J Nanomedicine. 2017;12:3267-3280 pubmed publisher
    ..These findings may aid in the optimization of hierarchical biomaterial topographies targeting Hedgehog-Gli1 signaling. ..
  3. Yoshida T, Hamano A, Ueda A, Takeuchi H, Yamaoka S. Human SMOOTHENED inhibits human immunodeficiency virus type 1 infection. Biochem Biophys Res Commun. 2017;493:132-138 pubmed publisher
    ..These results suggest that SMO inhibits HIV-1 replication after completion of reverse transcription but before integration. ..
  4. Mollereau B. Establishing links between endoplasmic reticulum-mediated hormesis and cancer. Mol Cell Biol. 2013;33:2372-4 pubmed publisher
  5. Shi X, Garcia G, Van De Weghe J, McGorty R, Pazour G, Doherty D, et al. Super-resolution microscopy reveals that disruption of ciliary transition-zone architecture causes Joubert syndrome. Nat Cell Biol. 2017;19:1178-1188 pubmed publisher
    ..We propose that the disruption of transition-zone architecture in JBTS leads to a failure of SMO to accumulate at the transition zone and cilium, disrupting developmental signalling in JBTS. ..
  6. Monkkonen T, Landua J, Visbal A, Lewis M. Epithelial and non-epithelial Ptch1 play opposing roles to regulate proliferation and morphogenesis of the mouse mammary gland. Development. 2017;144:1317-1327 pubmed publisher
  7. Bohnenpoll T, Wittern A, Mamo T, Weiss A, Rudat C, Kleppa M, et al. A SHH-FOXF1-BMP4 signaling axis regulating growth and differentiation of epithelial and mesenchymal tissues in ureter development. PLoS Genet. 2017;13:e1006951 pubmed publisher
  8. Huang J, Reilein A, Kalderon D. Yorkie and Hedgehog independently restrict BMP production in escort cells to permit germline differentiation in the Drosophila ovary. Development. 2017;144:2584-2594 pubmed publisher
    ..Thus, both the coupling and output of the Hh and Yki signaling pathways differ between FSCs and ECs despite their proximity and the fact that FSCs give rise directly to ECs. ..
  9. Rosow D, Liss A, Strobel O, Fritz S, Bausch D, Valsangkar N, et al. Sonic Hedgehog in pancreatic cancer: from bench to bedside, then back to the bench. Surgery. 2012;152:S19-32 pubmed publisher

More Information


  1. Shao J, Xu L, Chen L, Lu Q, Xie X, Shi W, et al. Arl13b Promotes Gastric Tumorigenesis by Regulating Smo Trafficking and Activation of the Hedgehog Signaling Pathway. Cancer Res. 2017;77:4000-4013 pubmed publisher
    ..Our results show how Arl13b participates in Hh pathway activation in gastric cancer. Cancer Res; 77(15); 4000-13. ©2017 AACR. ..
  2. Monis W, Faundez V, Pazour G. BLOC-1 is required for selective membrane protein trafficking from endosomes to primary cilia. J Cell Biol. 2017;216:2131-2150 pubmed publisher
    ..This is the first demonstration of a role for BLOC-1 in ciliary assembly and highlights the complexity of pathways taken to the cilium. ..
  3. Schwalbe E, Lindsey J, Nakjang S, Crosier S, Smith A, Hicks D, et al. Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: a cohort study. Lancet Oncol. 2017;18:958-971 pubmed publisher
  4. Zhu S, Huang J, Peng W, Wu D, Luo M, Li Q, et al. Inhibition of smoothened decreases proliferation of synoviocytes in rheumatoid arthritis. Cell Mol Immunol. 2017;14:214-222 pubmed publisher
    ..05). The results suggest that Shh signaling plays an important role in RA-FLSs proliferation in a Smo-dependent manner and may contribute to synovial hyperplasia. Targeting Shh signaling may help control joint damage in patients with RA. ..
  5. Dagklis A, Pauwels D, Lahortiga I, Geerdens E, Bittoun E, Cauwelier B, et al. Hedgehog pathway mutations in T-cell acute lymphoblastic leukemia. Haematologica. 2015;100:e102-5 pubmed publisher
  6. Xiao X, Tang J, Peng C, Wang Y, Fu L, Qiu Z, et al. Cholesterol Modification of Smoothened Is Required for Hedgehog Signaling. Mol Cell. 2017;66:154-162.e10 pubmed publisher
    ..Together, the results of our study suggest that Hh signaling transduces to SMO through modulating its cholesterylation and provides a therapeutic opportunity to treat Hh-pathway-related cancers by targeting SMO cholesterylation. ..
  7. Sahm F, Schrimpf D, Stichel D, Jones D, Hielscher T, Schefzyk S, et al. DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis. Lancet Oncol. 2017;18:682-694 pubmed publisher
    ..German Cancer Aid, Else Kröner-Fresenius Foundation, and DKFZ/Heidelberg Institute of Personalized Oncology/Precision Oncology Program. ..
  8. Yang Z, Lv Y, Wang L, Chen Y, Han J, Zhao S, et al. Inhibition of hedgehog pathway reveals the regulatory role of SMO in gastric cancer cells. Tumour Biol. 2017;39:1010428317715546 pubmed publisher
    ..Our studies demonstrate an important role for smoothened and glioma-associated oncogene homology-1 in gastric cancer and suggest inhibition of hedgehog pathway as a novel and potent strategy to treat gastric cancer patients. ..
  9. Morgillo F, Amendola G, Della Corte C, Giacomelli C, Botta L, Di Maro S, et al. Dual MET and SMO Negative Modulators Overcome Resistance to EGFR Inhibitors in Human Nonsmall Cell Lung Cancer. J Med Chem. 2017;60:7447-7458 pubmed publisher
    ..The identification of the known MET TKIs, glesatinib and foretinib, as negative modulators of the Hh pathway, widens their application in the context of NSCLC. ..
  10. Hidalgo M, Maitra A. The hedgehog pathway and pancreatic cancer. N Engl J Med. 2009;361:2094-6 pubmed publisher
  11. Chaudhry P, Singh M, Triche T, Guzman M, Merchant A. GLI3 repressor determines Hedgehog pathway activation and is required for response to SMO antagonist glasdegib in AML. Blood. 2017;129:3465-3475 pubmed publisher
    ..Furthermore, these data support rational combinations of hypomethylating agents with SMO antagonists in clinical trials. ..
  12. Wu F, Zhang Y, Sun B, McMahon A, Wang Y. Hedgehog Signaling: From Basic Biology to Cancer Therapy. Cell Chem Biol. 2017;24:252-280 pubmed publisher
    ..We discuss experiences and lessons learned from the decades-long efforts toward the development of cancer therapies targeting the HH pathway. Challenges to develop next-generation cancer therapies are highlighted. ..