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Updated: Apr 15, 2026
Tumor Allotransplantation in Drosophila melanogaster with a Programmable Auto-Nanoliter Injector
Published on: February 2, 2021
Malignant Drosophila tumors interrupt insulin signaling to induce cachexia-like wasting
Alejandra Figueroa-Clarevega1, David Bilder1
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
Abstract:
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.
Insights
Malignant tumors cause systemic wasting in distant tissues by secreting ImpL2, an insulin growth factor binding protein (IGFBP). This secreted factor induces insulin resistance, leading to tissue loss and cachexia-like symptoms.
Area of Science:
- Cancer Biology
- Endocrinology
- Drosophila melanogaster research
Background:
- Cancer cachexia involves systemic tissue wasting, driven by poorly understood long-range tumor interactions.
- Malignant tumors, not benign ones, induce significant wasting in distant adipose, muscle, and gonadal tissues.
Purpose of the Study:
- To investigate the mechanisms of long-range pathophysiological interactions between tumors and distant tissues.
- To identify secreted factors responsible for tumor-induced systemic wasting.
Main Methods:
- Utilized a Drosophila tumor transplantation model to study tumor-host interactions.
- Identified secreted factors using genetic screens and functional assays.
- Measured insulin signaling activity in peripheral tissues of tumor-bearing hosts.
Main Results:
- Discovered that the insulin growth factor binding protein (IGFBP) homolog ImpL2 is a key secreted factor mediating tumor-induced wasting.
- Demonstrated that ImpL2 is sufficient to cause tissue loss and reduces insulin activity in peripheral tissues.
- Showed that tumor-specific knockdown of ImpL2 significantly ameliorates wasting phenotypes.
Conclusions:
- Tumor-secreted ImpL2 acts as an antagonist of insulin signaling, inducing insulin resistance in distant tissues.
- This mechanism explains the systemic wasting and cachexia-like symptoms observed in cancer patients.
- Targeting tumor-secreted IGFBPs offers a potential therapeutic strategy for managing cancer cachexia.
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