title: Wildtype adult stem cells, unlike tumor cells, are resistant to cellular damages in Drosophila.
abstract: Adult stem cells or residential progenitor cells are critical to maintain the structure and function of adult tissues (homeostasis) throughout the lifetime of an individual. Mis-regulation of stem cell proliferation and differentiation often leads to diseases including cancer, however, how wildtype adult stem cells and cancer cells respond to cellular damages remains unclear. We find that in the adult Drosophila midgut, intestinal stem cells (ISCs), unlike tumor intestinal cells, are resistant to various cellular damages. Tumor intestinal cells, unlike wildtype ISCs, are easily eliminated by apoptosis. Further, their proliferation is inhibited upon autophagy induction, and autophagy-mediated tumor inhibition is independent of caspase-dependent apoptosis. Interestingly, inhibition of tumorigenesis by autophagy is likely through the sequestration and degradation of mitochondria, as compromising mitochondria activity in these tumor models mimics the induction of autophagy and increasing the production of mitochondria alleviates the tumor-suppression capacity of autophagy. Together, these data demonstrate that wildtype adult stem cells and tumor cells show dramatic differences in sensitivity to cellular damages, thus providing potential therapeutic implications targeting tumorigenesis.
authors: College of Life Sciences, Capital Normal University, Beijing 100048, China.
authors: Meifang
authors: M
authors: Ma
authors: College of Life Sciences, Capital Normal University, Beijing 100048, China.
authors: Hang
authors: H
authors: Zhao
authors: College of Life Sciences, Capital Normal University, Beijing 100048, China.
authors: Hanfei
authors: H
authors: Zhao
authors: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors: Richard
authors: R
authors: Binari
authors: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
authors: Norbert
authors: N
authors: Perrimon
authors: College of Life Sciences, Capital Normal University, Beijing 100048, China. Electronic address: zhli@cnu.edu.cn.
authors: Zhouhua
authors: Z
authors: Li
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology*; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D003433:Crosses, Genetic; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology*; D020287:In Situ Nick-End Labeling; D007414:Intestinal Neoplasms / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D009840:Oligomycins / Q000737:chemistry; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D009840:Oligomycins; D019908:Proto-Oncogene Proteins c-raf; D020169:Caspases
keywords: Apoptosis; Autophagy; Drosophila; Mitochondria; Raf; Stem cell; Tumorigenesis