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

INTRODUCTION: 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. METHODS: Here, we utilize Drosophila melanogaster and mole...

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Detalles Bibliográficos
Autores principales: Khalili, Dilan, Kunc, Martin, Herbrich, Sarah, Müller, Anna M., Theopold, Ulrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175591/
https://www.ncbi.nlm.nih.gov/pubmed/37188187
http://dx.doi.org/10.3389/fonc.2023.1170122
Descripción
Sumario:INTRODUCTION: 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. METHODS: Here, we utilize Drosophila melanogaster and molecular genetics to investigate the function of CLPs (imaginal disc growth factors; Idgf’s) in Ras(V12) dysplastic salivary glands. RESULTS AND DISCUSSION: 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, aSpectrin, which localizes to the EnVs. Our data provide new insight into CLP function in tumors and identifies specific targets for tumor control.