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Hyperinsulinemia Drives Epithelial Tumorigenesis by Abrogating Cell Competition
Yuya Sanaki1, Rina Nagata1, Daisuke Kizawa1
1Laboratory of Genetics, Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho, Sakyo-ku, Kyoto 606-8501, Japan.
Developmental Cell
|May 11, 2020
Summary
Metabolic diseases like type 2 diabetes increase cancer risk. This study reveals hyperinsulinemia promotes tumor growth by disrupting cell competition, linking metabolic health to cancer via insulin signaling.
Area of Science:
- Developmental Biology
- Metabolic Diseases
- Cancer Biology
Background:
- Metabolic diseases, including type 2 diabetes, are linked to higher cancer incidence.
- Cell competition is a mechanism where detrimental cells are eliminated by surrounding healthy cells.
Purpose of the Study:
- To investigate the mechanistic link between hyperinsulinemia and epithelial tumorigenesis.
- To explore the role of cell competition in metabolic disease-associated cancer.
Main Methods:
- Utilized Drosophila eye imaginal epithelium as a model system.
- Conducted genetic screens to identify genes involved in cell competition regulation.
- Investigated the role of insulin signaling and protein synthesis in tumorigenesis.
Main Results:
- Hyperinsulinemia abrogates cell competition, allowing oncogenic scribble (scrib) mutant cells to form tumors.
- Downregulation of insulin receptor substrate chico in brain insulin-producing cells (IPCs) leads to hyperinsulinemia and promotes tumorigenesis.
- Increased insulin levels, diet-induced or otherwise, trigger tumorigenesis; inhibiting protein synthesis prevents this overgrowth.
Conclusions:
- Systemic insulin regulation of cell competition provides a mechanistic link between metabolic disease and cancer risk.
- Hyperinsulinemia promotes epithelial tumorigenesis by boosting protein synthesis in pre-cancerous cells.
- Targeting insulin and protein synthesis pathways may offer therapeutic strategies for metabolic disease-associated cancers.
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