title: Translating Hedgehog in Cancer: Controlling Protein Synthesis.
abstract: Developmental Hedgehog (Hh) signaling is found deregulated in a broad spectrum of human malignancies and, thus, is an attractive target for cancer therapy. Currently available Hh inhibitors have shown the rapid occurrence of drug resistance, due to altered signaling in collateral pathways. Emerging observations suggest that Hh signaling regulates protein translation in pathways that depend both on Cap- and IRES-mediated translation. In addition, translational regulators have been shown to modulate Hh function. In this opinion, we describe this novel Hh/translation crosstalk and argue that it plays a relevant role in Hh-mediated tumorigenesis and drug resistance. As such, we suggest that drugs targeting translation might be introduced in novel protocols aimed at treating malignancies driven by aberrant Hh signaling.
authors: Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors: Davide
authors: D
authors: D'Amico
authors: Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy. Electronic address: gianluca.canettieri@uniroma1.it.
authors: Gianluca
authors: G
authors: Canettieri
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D055808:Drug Discovery / Q000379:methods; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D000067556:Internal Ribosome Entry Sites / Q000187:drug effects; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D000067556:Internal Ribosome Entry Sites; D012333:RNA, Messenger
keywords: Cancer; Cap; Hedgehog; IRES; translation