Autophagy and modular restructuring of metabolism control germline tumor differentiation and proliferation in C. elegans. Issue 3 (3rd March 2016)

• Record Type: Journal Article
• Authors: Gomes, Ligia C.; Odedra, Devang; Dikic, Ivan; Pohl, Christian
• Is Part Of: Autophagy. Volume 12:Issue 3(2016)
• Page Start: 529
• Page End: 546
• Publication Date: 2016-03-03
• Subjects: Autophagy -- C. elegans -- differentiation -- fasting -- life span -- metabolism -- nuclear hormone receptors -- ROS -- stress response -- teratoma; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2015.1136771
• Languages: English
• ISSNs: 1554-8627

Abstract

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.