Identification and characterization of novel gene networks connecting cancer and aging

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Adult stem cells are exposed to environmental stress and intracellular damages that go together with the process of aging. Longevity seems to be associated with increased renewal capacity via stem cells but also with increased cancer risk. In contrast, aging is associated with disturbance in stem cell number or function. This trade-off between longevity (aging) and cancer is further strengthened by findings that several solid cancer types harbor cancer stem cells that may derive from normal stem- or progenitor cells. Cancer stem cells are likely to contribute to therapy resistance and tumor relapse. This fellowship proposal stems from the identification of two aging-related genes Indy and krüppel homolog 1 (kr-h1) as enhancers of malignant growth in a high throughput unbiased gain-of-expression genetic screen in Drosophila. I noted that flies bearing kr-h1-induced tumors die 24 hours after eclosion with defects reminiscent to aged flies. The proposed work aims to identify the mechanism behind these observations using well-established Drosophila genetics, molecular biology and biochemistry. Particularly, I intend to take advantage of quantitative mass spectrometry and propose to identify, through genome and proteome-wide analyses, Indy and/or kr-h1 gene networks that have differential function or expression in young and aged flies in stem cell compartments. Results from quantitative mass spectrometry will be further investigated in a Drosophila tumor paradigm and in human cancer cells. These studies will help to identify common networks of the currently separated research fields of aging and cancer.