Primers on Molecular Pathways GLI: More than Just Hedgehog?

• Published in: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2008-01, Vol.8 (3), p.227-229
• Main Author: Fernández-Zapico, Martín E
• Format: Article
• Language: English
• Subjects: Animals; Drosophila melanogaster; Drosophila Proteins - physiology; Endocrinology & Metabolism; Gastroenterology and Hepatology; GLI proteins; Hedgehog; Hedgehog Proteins - physiology; Humans; Kruppel-Like Transcription Factors - physiology; Molecular Pathways; Nuclear Proteins - physiology; Pancreatic cancer; Pancreatic Neoplasms - etiology; Receptors, Cell Surface - physiology; Receptors, G-Protein-Coupled - physiology; Repressor Proteins - physiology; Signal Transduction; Smoothened Receptor; Transcription Factors - physiology; Zinc Finger Protein GLI1; Zinc Finger Protein Gli2
• ISSN: 1424-3903; 1424-3911
• DOI: 10.1159/000134271

Abstract GLI proteins, highly conserved in vertebrates and invertebrates, are critical in modulating embryonic development and adult tissue homeostasis. These proteins are zinc-finger-containing transcription factors that were originally identified by genetic screening of embryonic lethal mutants of Drosophila melanogaster . Alterations in GLI activity can lead to tumor development in tissues of different origin including the pancreas. GLI activity is mainly regulated by the Hedgehog pathway, via a ligand-receptor complex that triggers a signaling cascade that activates GLI transcription factors, which in turn regulate gene expression, an essential step of Hegdehog-mediated cellular effects. Interestingly, recent reports show the ability of other signaling cascades to modulate GLI function in cancer cells including RAS and TGF-β, two pathways implicated in pancreatic carcinogenesis.Thus, these findings suggest that GLI proteins are not an exclusive downstream target of Hedgehog but rather a common effector of a network of signaling pathways controlling pancreatic Carcinogenesis.