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

Autori
Škoda, Ana Marija ; Šimović, Dora ; Karin, Valentina ; Kardum, Vedran ; Vranić, Semir ; Šerman, Ljiljana

Izvornik
Bosnian journal of basic medical sciences (1512-8601) 18 (2018), 1; 8-20

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, znanstveni

Ključne riječi
Hedgehog signaling pathway ; Hh ; tumorigenesis ; signal transduction

Sažetak
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, Suppressor of fused homolog, kinesin-7, protein kinase A, and cyclic adenosine monophosphate (AMP). 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.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

Napomena
This publication was co-financed by the European
Union through the Europe Regional Development
Fund, Operational Programme Competitiveness and
Cohesion, under grant agreement No.
KK.01.1.1.01.0008, Reproductive and Regenerative
Medicine - Exploring New Platforms and Potentials

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