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

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

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1170122

DOI=10.3389/fonc.2023.1170122

ISSN=2234-943X

ABSTRACT=<sec><title>Introduction</title><p>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. </p></sec><sec><title>Methods</title><p>Here, we utilize <italic>Drosophila melanogaster</italic> and molecular genetics to investigate the function of CLPs (imaginal disc growth factors; Idgf’s) in <italic>Ras<sup>V12</sup></italic> dysplastic salivary glands. </p></sec><sec><title>Results and discussion</title><p>We find one of the Idgf’s members, <italic>Idgf3</italic>, is transcriptionally induced in a JNK-dependent manner via a positive feedback loop mediated by reactive oxygen species (ROS). Moreover, <italic>Idgf3</italic> accumulates in enlarged endosomal vesicles (EnVs) that promote tumor progression by disrupting cytoskeletal organization. The process is mediated <italic>via</italic> 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.</p></sec>