title: A curated census of autophagy-modulating proteins and small molecules: candidate targets for cancer therapy.
abstract: Autophagy, a programmed process in which cell contents are delivered to lysosomes for degradation, appears to have both tumor-suppressive and tumor-promoting functions; both stimulation and inhibition of autophagy have been reported to induce cancer cell death, and particular genes and proteins have been associated both positively and negatively with autophagy. To provide a basis for incisive analysis of those complexities and ambiguities and to guide development of new autophagy-targeted treatments for cancer, we have compiled a comprehensive, curated inventory of autophagy modulators by integrating information from published siRNA screens, multiple pathway analysis algorithms, and extensive, manually curated text-mining of the literature. The resulting inventory includes 739 proteins and 385 chemicals (including drugs, small molecules, and metabolites). Because autophagy is still at an early stage of investigation, we provide extensive analysis of our sources of information and their complex relationships with each other. We conclude with a discussion of novel strategies that could potentially be used to target autophagy for cancer therapy.
authors.affiliation: Department of Bioinformatics and Computational Biology; The University of Texas MD Anderson Cancer Center; Houston, TX USA.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Lorenzi
authors.affiliation: Department of Systems Biology; The University of Texas MD Anderson Cancer Center; Houston, TX USA.
authors.forename: Sofie
authors.initials: S
authors.lastname: Claerhout
authors.affiliation: Department of Systems Biology; The University of Texas MD Anderson Cancer Center; Houston, TX USA.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.affiliation: Department of Bioinformatics and Computational Biology; The University of Texas MD Anderson Cancer Center; Houston, TX USA; Department of Systems Biology; The University of Texas MD Anderson Cancer Center; Houston, TX USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Weinstein
mesh_terms: D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D056726:Genetic Association Studies; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D034741:RNA, Small Interfering / Q000378:metabolism; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D034741:RNA, Small Interfering; D054852:Small Molecule Libraries
keywords: L-asparaginase; RNAi; autophagy; cancer; high-throughput screening; natural language processing; pathway analysis; siRNA; text-mining