The role of the Hedgehog signaling pathway in cancer: A comprehensive review.
Author | Skoda, Ana Marija |
Author | Simovic, Dora |
Author | Karin, Valentina |
Author | Kardum, Vedran |
Author | Vranic, Semir |
Author | Serman, Ljiljana |
Available date | 2019-04-03T11:42:23Z |
Publication Date | 2018-02-01 |
Publication Name | Bosnian Journal of Basic Medical Science |
Identifier | http://dx.doi.org/10.17305/bjbms.2018.2756 |
Citation | Skoda AM, Simovic D, Karin V, Kardum V, Vranic S, Serman L. The role of the Hedgehog signaling pathway in cancer: A comprehensive review. Bosn J of Basic Med Sci [Internet]. 2018Feb.20 [cited 2019Apr.3];18(1):8-20. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/2756 |
ISSN | 1512-8601 |
Abstract | 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. |
Language | en |
Publisher | Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina |
Subject | Hedgehog pathway cancer Hedgehog signaling pathway Hh tumorigenesis signal transduction |
Type | Article |
Issue Number | 1 |
Volume Number | 18 |
ESSN | 1840-4812 |
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