Chitinase-like proteins promoting tumorigenesis through disruption of cell polarity via enlarged endosomal vesicles

Dilan Khalili, Martin Kunc, Sarah Herbrich, Anna M Müller, Ulrich Theopold

Abstract

Introduction: Chitinase-like proteins (CLPs) are associated with tissue-remodeling and inflammation but also with several disorders, including fibrosis, atherosclerosis, allergies, and cancer. However, CLP's role in tumors is far from clear.

Methods: Here, we utilize Drosophila melanogaster and molecular genetics to investigate the function of CLPs (imaginal disc growth factors; Idgf's) in RasV12 dysplastic salivary glands.

Results and discussion: We find one of the Idgf's members, Idgf3, is transcriptionally induced in a JNK-dependent manner via a positive feedback loop mediated by reactive oxygen species (ROS). Moreover, Idgf3 accumulates in enlarged endosomal vesicles (EnVs) that promote tumor progression by disrupting cytoskeletal organization. The process is mediated via the downstream component, aSpectrin, which localizes to the EnVs. Our data provide new insight into CLP function in tumors and identifies specific targets for tumor control.

Keywords: Drosophila; chitinase; endosomal vesicles; immunity; insect immunity; salivary glands; tumor.

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Schematic summary how a Drosophila chitinase-like protein (Idgf3) contributes to the formation of enlarged vesicles in a fly tumor model.