Reference - Detail
|Author||Figueroa-Clarevega A, Bilder D.|
|Title||Malignant Drosophila tumors interrupt insulin signaling to induce cachexia-like wasting.|
Tumors kill patients not only through well-characterized perturbations to their local environment but also through poorly understood pathophysiological interactions with distant tissues. Here, we use a Drosophila tumor model to investigate the elusive mechanisms underlying such long-range interactions. Transplantation of tumors into adults induces robust wasting of adipose, muscle, and gonadal tissues that are distant from the tumor, phenotypes that resemble the cancer cachexia seen in human patients. Notably, malignant, but not benign, tumors induce peripheral wasting. We identify the insulin growth factor binding protein (IGFBP) homolog ImpL2, an antagonist of insulin signaling, as a secreted factor mediating wasting. ImpL2 is sufficient to drive tissue loss, and insulin activity is reduced in peripheral tissues of tumor-bearing hosts. Importantly, knocking down ImpL2, specifically in the tumor, ameliorates wasting phenotypes. We propose that the tumor-secreted IGFBP creates insulin resistance in distant tissues, thus driving a systemic wasting response.
|MeSH||Adenosine Triphosphate / metabolism Adipose Tissue / metabolism Adipose Tissue / pathology Animals Blotting, Western Cachexia / etiology* Cachexia / metabolism Cachexia / pathology Cells, Cultured Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism* Female Humans Image Processing, Computer-Assisted Insulin / metabolism* Muscle, Skeletal / metabolism Muscle, Skeletal / pathology Neoplasms, Experimental / complications* Neoplasms, Experimental / metabolism Neoplasms, Experimental / pathology Nuclear Proteins / genetics Nuclear Proteins / metabolism* Ovary / metabolism Ovary / pathology Phenotype RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Trans-Activators / genetics Trans-Activators / metabolism*|
|WOS Category||DEVELOPMENTAL BIOLOGY CELL BIOLOGY|