RRC ID 70721
著者 Jevitt A, Huang YC, Zhang SM, Chatterjee D, Wang XF, Xie GQ, Deng WM.
タイトル Modeling Notch-Induced Tumor Cell Survival in the Drosophila Ovary Identifies Cellular and Transcriptional Response to Nuclear NICD Accumulation.
ジャーナル Cells
Abstract Notch is a conserved developmental signaling pathway that is dysregulated in many cancer types, most often through constitutive activation. Tumor cells with nuclear accumulation of the active Notch receptor, NICD, generally exhibit enhanced survival while patients experience poorer outcomes. To understand the impact of NICD accumulation during tumorigenesis, we developed a tumor model using the Drosophila ovarian follicular epithelium. Using this system we demonstrated that NICD accumulation contributed to larger tumor growth, reduced apoptosis, increased nuclear size, and fewer incidents of DNA damage without altering ploidy. Using bulk RNA sequencing we identified key genes involved in both a pre- and post- tumor response to NICD accumulation. Among these are genes involved in regulating double-strand break repair, chromosome organization, metabolism, like raptor, which we experimentally validated contributes to early Notch-induced tumor growth. Finally, using single-cell RNA sequencing we identified follicle cell-specific targets in NICD-overexpressing cells which contribute to DNA repair and negative regulation of apoptosis. This valuable tumor model for nuclear NICD accumulation in adult Drosophila follicle cells has allowed us to better understand the specific contribution of nuclear NICD accumulation to cell survival in tumorigenesis and tumor progression.
巻・号 10(9)
公開日 2021-8-27
DOI 10.3390/cells10092222
PII cells10092222
PMID 34571871
PMC PMC8465586
MeSH Animals Carcinogenesis / genetics Carcinogenesis / pathology Cell Nucleus / genetics* Cell Survival / genetics* DNA Repair / genetics Drosophila / genetics* Drosophila Proteins / genetics* Female Ovary / pathology* Receptor, Notch1 / genetics Receptors, Notch / genetics* Signal Transduction / genetics Transcription, Genetic / genetics*
IF 4.366
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