Chitinase-like proteins promoting tumorigenesis through disruption of cell polarity via enlarged endosomal 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. We find one of the Idgf's members, Idgf3, is transcriptionally induced tissue and cell-autonomously and in a non-canonical JNK-dependent manner via a positive feedback loop mediated by reactive oxygen species (ROS). Moreover, Idgf3 accumulates in enlarged endosomal vesicles (EVs) that promote tumor progression by disrupting cytoskeletal organization, independent of Rab5 and Rab11. The process is mediated via Rac1 and the downstream component, αSpectrin, localized to the EVs. Our data provide new insight into tissue-autonomous CLP function in tumors and identifies specific targets for tumor control.  

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

CLP

Idgf3

spectrin

tumor

endosomes.

Publication and Content Type

vet (subject category)

ovr (subject category)