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Autophagy Promotes Tumor-like Stem Cell Niche Occupancy.


ABSTRACT: Adult stem cells usually reside in specialized niche microenvironments. Accumulating evidence indicates that competitive niche occupancy favors stem cells with oncogenic mutations, also known as tumor-like stem cells. However, the mechanisms that regulate tumor-like stem cell niche occupancy are largely unknown. Here, we use Drosophila ovarian germline stem cells as a model and use bam mutant cells as tumor-like stem cells. Interestingly, we find that autophagy is low in wild-type stem cells but elevated in bam mutant stem cells. Significantly, autophagy is required for niche occupancy by bam mutant stem cells. Although loss of either atg6 or Fip200 alone in stem cells does not impact their competitiveness, loss of these conserved regulators of autophagy decreases bam mutant stem cell niche occupancy. In addition, starvation enhances the competition of bam mutant stem cells for niche occupancy in an autophagy-dependent manner. Of note, loss of autophagy slows the cell cycle of bam mutant stem cells and does not influence stem cell death. In contrast to canonical epithelial cell competition, loss of regulators of tissue growth, either the insulin receptor or cyclin-dependent kinase 2 function, influences the competition of bam mutant stem cells for niche occupancy. Additionally, autophagy promotes the tumor-like growth of bam mutant ovaries. Autophagy is known to be induced in a wide variety of tumors. Therefore, these results suggest that specifically targeting autophagy in tumor-like stem cells has potential as a therapeutic strategy.

SUBMITTER: Zhao S 

PROVIDER: S-EPMC6185742 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Autophagy Promotes Tumor-like Stem Cell Niche Occupancy.

Zhao Shaowei S   Fortier Tina M TM   Baehrecke Eric H EH  

Current biology : CB 20180927 19


Adult stem cells usually reside in specialized niche microenvironments. Accumulating evidence indicates that competitive niche occupancy favors stem cells with oncogenic mutations, also known as tumor-like stem cells. However, the mechanisms that regulate tumor-like stem cell niche occupancy are largely unknown. Here, we use Drosophila ovarian germline stem cells as a model and use bam mutant cells as tumor-like stem cells. Interestingly, we find that autophagy is low in wild-type stem cells but  ...[more]

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