Chitinase-like protein promotes tumorigenesis through disruption of cell polarity via enlarged vesicles

Chitinase-like proteins (CLPs) are associated with tissue-remodelling and inflammation but also with several disorders, including fibrosis, atherosclerosis, allergies, and cancer. However, the CLP’s role in tumors is far from clear. Here, we utilize Drosophila melanogaster to investigate the function of CLPs (imaginal disc growth factors; Idgf’s) in RasV12 dysplastic salivary glands (SGs). We find one of the Idgf’s members, Idgf3, to be transcriptionally induced in a tissue- and cell-autonomously manner in a Drosophila hypertrophic model for early tumor progression. Induction involves non-canonical JNK-signaling via a positive feedback loop mediated by reactive oxygen species (ROS). Moreover, Idgf3 accumulates in enlarged vesicles (EnVs) that promote tumor progression by disrupting cytoskeletal organization, independent of Rab5 and Rab11. The process is mediated via Rac1 and the downstream component, αSpectrin, which localizes to the EnVs. Similar to Idgf3, expression of two human members of the CLP family in Drosophila SGs aggravates tumor-related phenotypes. Our data provide new insight into a phylogenetically conserved tissue-autonomous CLP function in tumors and identify specific targets for tumor control.