title: Autophagy and modular restructuring of metabolism control germline tumor differentiation and proliferation in C. elegans.
abstract: Autophagy can act either as a tumor suppressor or as a survival mechanism for established tumors. To understand how autophagy plays this dual role in cancer, in vivo models are required. By using a highly heterogeneous C. elegans germline tumor, we show that autophagy-related proteins are expressed in a specific subset of tumor cells, neurons. Inhibition of autophagy impairs neuronal differentiation and increases tumor cell number, resulting in a shorter life span of animals with tumors, while induction of autophagy extends their life span by impairing tumor proliferation. Fasting of animals with fully developed tumors leads to a doubling of their life span, which depends on modular changes in transcription including switches in transcription factor networks and mitochondrial metabolism. Hence, our results suggest that metabolic restructuring, cell-type specific regulation of autophagy and neuronal differentiation constitute central pathways preventing growth of heterogeneous tumors.
authors.affiliation: a Buchmann Institute for Molecular Life Sciences, Goethe University , Frankfurt (Main) , Germany.|b Institute of Biochemistry II, School of Medicine, Goethe University , Frankfurt (Main) , Germany.
authors.forename: Ligia C
authors.initials: LC
authors.lastname: Gomes
authors.affiliation: a Buchmann Institute for Molecular Life Sciences, Goethe University , Frankfurt (Main) , Germany.|b Institute of Biochemistry II, School of Medicine, Goethe University , Frankfurt (Main) , Germany.
authors.forename: Devang
authors.initials: D
authors.lastname: Odedra
authors.affiliation: a Buchmann Institute for Molecular Life Sciences, Goethe University , Frankfurt (Main) , Germany.|b Institute of Biochemistry II, School of Medicine, Goethe University , Frankfurt (Main) , Germany.|c Department of Immunology and Medical Genetics , University of Split, School of Medicine , Split , Croatia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Dikic
authors.affiliation: a Buchmann Institute for Molecular Life Sciences, Goethe University , Frankfurt (Main) , Germany.|b Institute of Biochemistry II, School of Medicine, Goethe University , Frankfurt (Main) , Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Pohl
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001343:Autophagy / Q000235:genetics; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D005215:Fasting; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005854:Germ Cells; D008136:Longevity; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D017382:Reactive Oxygen Species
keywords: Autophagy; C. elegans; ROS; differentiation; fasting; life span; metabolism; nuclear hormone receptors; stress response; teratoma