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=Volume 13 - 2023

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=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. Here, we utilize the fruitfly Drosophila melanogaster to investigate the function of CLPs (imaginal disc growth factors; Idgf's) in RasV12 dysplastic salivary glands. 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, αSpectrin, which localizes to the EnVs. We observe similar phenotypes upon expression of human CLP members in our fly model indicating phylogenetic conservation.  Our data provide new insight into CLP function in tumors and identify specific targets for tumor control.