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Autophagy. 2016;12(3):529-46. doi: 10.1080/15548627.2015.1136771. Epub 2016 Jan 13.

Autophagy and modular restructuring of metabolism control germline tumor differentiation and proliferation in C. elegans.

Gomes LC1,2, Odedra D1,2, Dikic I1,2,3, Pohl C1,2.

Author information

1
a Buchmann Institute for Molecular Life Sciences, Goethe University , Frankfurt (Main) , Germany.
2
b Institute of Biochemistry II, School of Medicine, Goethe University , Frankfurt (Main) , Germany.
3
c Department of Immunology and Medical Genetics , University of Split, School of Medicine , Split , Croatia.

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.

KEYWORDS:

Autophagy; C. elegans; ROS; differentiation; fasting; life span; metabolism; nuclear hormone receptors; stress response; teratoma

PMID:
26759963
PMCID:
PMC4835962
DOI:
10.1080/15548627.2015.1136771
[Indexed for MEDLINE]
Free PMC Article

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