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PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of Colorectal Cancer Cells under Simulated Microgravity
Raj Pranap Arun, DIvya Sivanesan, Prasanna Vidyasekar,
Published in Nature Publishing Group
2017
PMID: 28729699
Volume: 7
   
Issue: 1
Abstract
Gravity is a major physical factor determining the stress and strain around cells. Both in space experiments and ground simulation, change in gravity impacts the viability and function of various types of cells as well as in vivo conditions. Cancer cells have been shown to die under microgravity. This can be exploited for better understanding of the biology and identification of novel avenues for therapeutic intervention. Here, we described the effect of microgravity simulated using Rotational Cell Culture System-High Aspect Ratio Vessel (RCCS-HARV) on the viability and morphological changes of colorectal cancer cells. We observed DLD1, HCT116 and SW620 cells die through apoptosis under simulated microgravity (SM). Gene expression analysis on DLD1 cells showed upregulation of tumor suppressors PTEN and FOXO3; leading to AKT downregulation and further induction of apoptosis, through upregulation of CDK inhibitors CDKN2B, CDKN2D. SM induced cell clumps had elevated hypoxia and mitochondrial membrane potential that led to adaptive responses like morphogenetic changes, migration and deregulated autophagy, when shifted to normal culture conditions. This can be exploited to understand the three-dimensional (3D) biology of cancer in the aspect of stress response. This study highlights the regulation of cell function and viability under microgravity through PTEN/FOXO3/AKT pathway. © 2017 The Author(s).
About the journal
JournalScientific Reports
PublisherNature Publishing Group
ISSN20452322
Open AccessYes
Concepts (24)
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    PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE
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    Protein kinase b
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    TRANSCRIPTION FACTOR FKHRL1
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    Cell aggregation
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    Cell cycle
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    Cell death
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    Cell differentiation
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    Cell motion
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    Cell proliferation
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    COLORECTAL TUMOR
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    Human
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    Metabolism
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    Pathology
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    Signal transduction
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    Tumor cell line
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    WEIGHTLESSNESS
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    Cell line, tumor
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    Cell movement
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    COLORECTAL NEOPLASMS
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    FORKHEAD BOX PROTEIN O3
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    Humans
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    Proto-oncogene proteins c-akt
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    PTEN PHOSPHOHYDROLASE
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    WEIGHTLESSNESS SIMULATION