Primers on molecular pathways GLI: more than just Hedgehog?
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 Hedgehog-mediated cellular effects. Interestingly, recent reports show the ability of other signaling cascades to modulate GLI function in cancer cells including RAS and TGF-beta, 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. and IAP.
Fernández-Zapico
Martín E
ME
Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, MN 55905, USA. fernandezzapico.martin@mayo.edu
D000818:Animals; D029721:Drosophila Proteins / Q000502:physiology; D004331:Drosophila melanogaster; D053823:Hedgehog Proteins / Q000502:physiology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000209:etiology; D011956:Receptors, Cell Surface / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology; D015398:Signal Transduction; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000502:physiology*; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2
D029721:Drosophila Proteins; C400551:GLI1 protein, human; C082593:GLI2 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; D000072086:Smoothened Receptor; C097059:Su(fu) protein, Drosophila; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; C070844:ptc protein, Drosophila; C100664:smo protein, Drosophila