Effect of weightlessness on cytoskeleton architecture and proliferation of human breast cancer cell line MCF‐7

Vassy, Jany; Portet, Stéphanie; Beil, Michael; Millot, Guy; Fauvel-Lafève, Françoise; Gasset, G.; Schöevaërt, Damien

doi:10.1096/fsb2fj000527fje

Cited by 27 publications

(42 citation statements)

References 43 publications

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“…In addition, the size of cells cultured under SMG was smaller than that of cells under ground condition ( Fig. 1B and C), consistent with a previous report [Vassy et al, 2001]. To examine potential alterations in the structure of cytoskeleton triggered by the exposure to SMG, we stained cells with FITClabeled anti-a-tubulin antibody or FITC-labeled phalloidin, and analyzed microtubules and microfilaments, respectively, by confocal microscopy.…”

Section: Simulated Microgravity Alters Cytoskeleton Structuresupporting

confidence: 89%

Simulated Microgravity Promotes Cell Apoptosis Through Suppressing Uev1A/TICAM/TRAF/NF‐κB‐Regulated Anti‐Apoptosis and p53/PCNA‐ and ATM/ATR‐Chk1/2‐Controlled DNA‐Damage Response Pathways

Zhao

Tang

Umeshappa

et al. 2016

J of Cellular Biochemistry

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Microgravity has been known to induce cell death. However, its underlying mechanism is less studied. In this study, BL6-10 melanoma cells were cultured in flasks under simulated microgravity (SMG). We examined cell apoptosis, and assessed expression of genes associated with apoptosis and genes regulating apoptosis in cells under SMG. We demonstrate that SMG induces cell morphological changes and microtubule alterations by confocal microscopy, and enhances apoptosis by flow cytometry, which was associated with up- and down-regulation of pro-apoptotic and anti-apoptotic genes, respectively. Moreover, up- and down-regulation of pro-apoptotic (Caspases 3, 7, 8) and anti-apoptotic (Bcl2 and Bnip3) molecules was confirmed by Western blotting analysis. Western blot analysis also indicates that SMG causes inhibition of an apoptosis suppressor, pNF-κB-p65, which is complemented by the predominant localization of NF-κB-p65 in the cytoplasm. SMG also reduces expression of molecules regulating the NF-κB pathway including Uev1A, TICAM, TRAF2, and TRAF6. Interestingly, 10 DNA repair genes are down-regulated in cells exposed to SMG, among which down-regulation of Parp, Ercc8, Rad23, Rad51, and Ku70 was confirmed by Western blotting analysis. In addition, we demonstrate a significant inhibition of molecules involved in the DNA-damage response, such as p53, PCNA, ATM/ATR, and Chk1/2. Taken together, our work reveals that SMG promotes the apoptotic response through a combined modulation of the Uev1A/TICAM/TRAF/NF-κB-regulated apoptosis and the p53/PCNA- and ATM/ATR-Chk1/2-controlled DNA-damage response pathways. Thus, our investigation provides novel information, which may help us to determine the cause of negative alterations in human physiology occurring at spaceflight environment. J. Cell. Biochem. 117: 2138-2148, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Simulated Microgravity Alters Cytoskeleton Structuresupporting

confidence: 89%

Simulated Microgravity Promotes Cell Apoptosis Through Suppressing Uev1A/TICAM/TRAF/NF‐κB‐Regulated Anti‐Apoptosis and p53/PCNA‐ and ATM/ATR‐Chk1/2‐Controlled DNA‐Damage Response Pathways

Zhao

Tang

Umeshappa

et al. 2016

J of Cellular Biochemistry

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“…36). In another study, changes in the cytokeratin network were reported for part of the cells after 48 h of microgravity (39).…”

Section: Experimental Observations Of Cytoskeletal Changes During Micmentioning

confidence: 94%

The role of the cytoskeleton in sensing changes in gravity by nonspecialized cells

et al. 2013

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A large body of evidence indicates that single cells in vitro respond to changes in gravity, and that this response might play an important role for physiological changes at the organism level during spaceflight. Gravity can lead to changes in cell proliferation, differentiation, signaling, and gene expression. At first glance, gravitational forces seem too small to affect bodies with the size of a cell. Thus, the initial response to gravity is both puzzling and important for understanding physiological changes in space. This also offers a unique environment to study the mechanical response of cells. In the past 2 decades, important steps have been made in the field of mechanobiology, and we use these advances to reevaluate the response of single cells to changes in gravity. Recent studies have focused on the cytoskeleton as initial gravity sensor. Thus, we review the observed changes in the cytoskeleton in a microgravity environment, both during spaceflight and in ground-based simulation techniques. We also evaluate to what degree the current experimental evidence supports the cytoskeleton as primary gravity sensor. Finally, we consider how the cytoskeleton itself could be affected by changed gravity. To make the next step toward understanding the response of cells to altered gravity, the challenge will be to track changes quantitatively and on short timescales.

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“…Microgravity induces adverse and metabolic effects in animals, humans and cellular systems [1][2][3][4]. We have evaluated the effects of microgravity on cell proliferation, glucose uptake, amino acid uptake and incorporation into proteins in neoplastic human breast cancer cells (MCF-7) and normal murine vascular smooth muscle cells (VSMC).…”

Section: Introductionmentioning

confidence: 99%

Exposure to modeled microgravity induces metabolic idleness in malignant human MCF‐7 and normal murine VSMC cells

et al. 2006

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We investigated the effect of modeled microgravity (MMG) on normal vascular smooth muscle cells (VSMC) and neoplastic human breast cancer cells (MCF-7). In both cell types, MMG induced partial arrest in G 2 M and increased p14-3-3, HSP70, HSP60 and p21 expression. Cells synchronized by 24 h starvation reentered the normal cycle within 24 h if released in complete medium and exposed to normal gravity, but not if exposed to MMG. Similarly, MMG prevented VSMC and MCF-7 cells from overcoming growth arrest and re-synthesizing DNA. This study shows that cells adjust their metabolic rate in response to MMG.

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Effect of weightlessness on cytoskeleton architecture and proliferation of human breast cancer cell line MCF‐7

Cited by 27 publications

References 43 publications

Simulated Microgravity Promotes Cell Apoptosis Through Suppressing Uev1A/TICAM/TRAF/NF‐κB‐Regulated Anti‐Apoptosis and p53/PCNA‐ and ATM/ATR‐Chk1/2‐Controlled DNA‐Damage Response Pathways

Simulated Microgravity Promotes Cell Apoptosis Through Suppressing Uev1A/TICAM/TRAF/NF‐κB‐Regulated Anti‐Apoptosis and p53/PCNA‐ and ATM/ATR‐Chk1/2‐Controlled DNA‐Damage Response Pathways

The role of the cytoskeleton in sensing changes in gravity by nonspecialized cells

Exposure to modeled microgravity induces metabolic idleness in malignant human MCF‐7 and normal murine VSMC cells

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