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

Abstract

AbstractChitinase-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 utilizeDrosophila melanogasterto investigate the function of CLPs (imaginal disc growth factors; Idgf’s) inRasV12dysplastic 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. Our data provide new insight into CLP function in tumors and identifies specific targets for tumor control.