Autophagy and modular restructuring of metabolism control germline tumor differentiation and proliferation in C. elegans
- 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.
Author: | Ligia G. Gomes, Devang OdedraORCiD, Ivan ĐikićORCiDGND, Christian PohlORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-425803 |
DOI: | https://doi.org/10.1080/15548627.2015.1136771 |
ISSN: | 1554-8635 |
ISSN: | 1554-8627 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/26759963 |
Parent Title (English): | Autophagy |
Publisher: | Taylor & Francis |
Place of publication: | Abingdon, Oxon |
Document Type: | Article |
Language: | English |
Year of Completion: | 2017 |
Date of first Publication: | 2016/01/13 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2017/01/16 |
Tag: | C. elegans; ROS; autophagy; differentiation; fasting; life span; metabolism; nuclear hormone receptor; stress response; teratoma |
Volume: | 12 |
Issue: | 3 |
Page Number: | 18 |
First Page: | 529 |
Last Page: | 546 |
HeBIS-PPN: | 425192717 |
Institutes: | Biowissenschaften / Biowissenschaften |
Medizin / Medizin | |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |