Skip to main content

Advertisement

Log in

Simulated microgravity inhibits the viability and migration of glioma via FAK/RhoA/Rock and FAK/Nek2 signaling

  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Abstract

Due to excessive proliferation and metastasis, glioma is the most common primary tumor in the central nervous system. Previous reports show simulated microgravity (SMG) has the ability to inhibit the proliferation and migration of cancer. The aim of this study was to evaluate the viability and migration of U251 cells in SMG environment. SMG induced apoptosis of U251 cells. The FAK/RhoA/Rock and FAK/Nek2 signaling events were attenuated by SMG to destabilize actin cytoskeleton and centrosome disjunction, which caused G2/M arrest and inhibition of cell viability and migration. Overexpressed FAK reversed SMG-induced inhibition of viability and migration in U251 cells, which increased downstream RhoA/Rock signaling and Nek2. These findings reveal novel pathways of FAK/RhoA/Rock and FAK/Nek2 are affected by SMG, and highlight an opportunity to expand therapeutic options in a variety of settings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
Figure 7.
Figure 8.

Similar content being viewed by others

References

  • Aleshcheva G, Bauer J, Hemmersbach R, Slumstrup L, Wehland M, Infanger M, Grimm D (2016) Scaffold-free tissue formation under real and simulated microgravity conditions. Basic Clin Pharmacol Toxicol 119(Suppl 3):26–33

    Article  CAS  PubMed  Google Scholar 

  • Arun RP, Sivanesan D, Vidyasekar P, Verma RS (2017) PTEN/FOXO3/AKT pathway regulates cell death and mediates morphogenetic differentiation of colorectal cancer cells under simulated microgravity. Sci Rep 7:5952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bayliss R, Fry A, Haq T, Yeoh S (2012) On the molecular mechanisms of mitotic kinase activation. Open Biol 2:120136

    Article  PubMed  PubMed Central  Google Scholar 

  • Beck M, Tabury K, Moreels M, Jacquet P, Van Oostveldt P, De Vos WH, Baatout S (2012) Simulated microgravity decreases apoptosis in fetal fibroblasts. Int J Mol Med 30:309–313

    Article  PubMed  Google Scholar 

  • Beck M, Moreels M, Quintens R, Abou-El-Ardat K, El-Saghire H, Tabury K, Michaux A, Janssen A, Neefs M, Van Oostveldt P, De Vos WH, Baatout S (2014) Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts. Int J Mol Med 34:606–615

    Article  CAS  PubMed  Google Scholar 

  • Benavides DT, Franco-Obregon A, Egli M (2013) Gravitational force modulates G2/M phase exit in mechanically unloaded myoblasts. Cell Cycle 12:3001–3012

    Article  CAS  Google Scholar 

  • Claro S, Oshiro ME, Mortara RA, Paredes-Gamero EJ, Pereira GJ, Smaili SS, Ferreira AT (2014) gamma-Rays-generated ROS induce apoptosis via mitochondrial and cell cycle alteration in smooth muscle cells. Int J Radiat Biol 90:914–927

    Article  CAS  PubMed  Google Scholar 

  • Dong Z, Lei Q, Yang R, Zhu S, Ke XX, Yang L, Cui H, Yi L (2017) Inhibition of neurotensin receptor 1 induces intrinsic apoptosis via let-7a-3p/Bcl-w axis in glioblastoma. Br J Cancer 116:1572–1584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Franco-Obregon A, Cambria E, Greutert H, Wernas T, Hitzl W, Egli M, Sekiguchi M, Boos N, Hausmann O, Ferguson SJ, Kobayashi H, Wuertz-Kozak K (2018) TRPC6 in simulated microgravity of intervertebral disc cells. Eur Spine J 27:2621–2630

    Article  PubMed  Google Scholar 

  • Ghasemi A, Hashemy SI, Aghaei M, Panjehpour M (2017) RhoA/ROCK pathway mediates leptin-induced uPA expression to promote cell invasion in ovarian cancer cells. Cell Signal 32:104–114

    Article  CAS  PubMed  Google Scholar 

  • Hetmanski JH, Schwartz JM, Caswell PT (2016) Modelling GTPase dynamics to understand RhoA-driven cancer cell invasion. Biochem Soc Trans 44:1695–1700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hughson RL, Helm A, Durante M (2018) Heart in space: effect of the extraterrestrial environment on the cardiovascular system. Nat Rev Cardiol 15:167–180

    Article  PubMed  Google Scholar 

  • Jiang M, Lyu Q, Bai YG, Liu H, Yang J, Cheng JH, Zheng M, Ma J (2018) Focal adhesions are involved in simulated-microgravity-induced basilar and femoral arterial remodeling in rats. Can J Physiol Pharmacol 96:772–782

    Article  CAS  PubMed  Google Scholar 

  • Lai XB, Nie YQ, Huang HL, Li YF, Cao CY, Yang H, Shen B, Feng ZQ (2017) NIMA-related kinase 2 regulates hepatocellular carcinoma cell growth and proliferation. Oncol Lett 13:1587–1594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li C, Gao S, Li X, Li C, Ma L (2018) Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA. Oncol Res 26:209–217

    Article  PubMed  Google Scholar 

  • Liu H, Liu B, Hou X, Pang B, Guo P, Jiang W, Ding Q, Zhang R, Xin T, Guo H, Xu S, Pang Q (2017) Overexpression of NIMA-related kinase 2 is associated with poor prognoses in malignant glioma. J Neuro-Oncol 132:409–417

    Article  CAS  Google Scholar 

  • Liu W, Chen Y, Meng J, Wu M, Bi F, Chang C, Li H, Zhang L (2018) Ablation of caspase-1 protects against TBI-induced pyroptosis in vitro and in vivo. J Neuroinflammation 15:48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McLean GW, Carragher NO, Avizienyte E, Evans J, Brunton VG, Frame MC (2005) The role of focal-adhesion kinase in cancer - a new therapeutic opportunity. Nat Rev Cancer 5:505–515

    Article  CAS  PubMed  Google Scholar 

  • Nam JH, Cho HJ, Kang H, Lee JY, Jung M, Chang YC, Kim K, Hoe HS (2017) A mercaptoacetamide-based class II histone deacetylase inhibitor suppresses cell migration and invasion in monomorphic malignant human glioma cells by inhibiting FAK/STAT3 signaling. J Cell Biochem 118:4672–4685

    Article  CAS  PubMed  Google Scholar 

  • Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2015) CBTRUS Statistical Report: primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. Neuro-Oncology 17(Suppl 4):iv1–iv62

    Article  PubMed  PubMed Central  Google Scholar 

  • Papaseit C, Pochon N, Tabony J (2000) Microtubule self-organization is gravity-dependent. Proc Natl Acad Sci U S A 97:8364–8368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ratushnyy AY, Buravkova LB (2017) Expression of focal adhesion genes in mesenchymal stem cells under simulated microgravity. Dokl Biochem Biophys 477:354–356

    Article  CAS  PubMed  Google Scholar 

  • Risin D, Pellis NR (2001) Modeled microgravity inhibits apoptosis in peripheral blood lymphocytes. In Vitro Cell Dev Biol Anim 37:66–72

    Article  CAS  PubMed  Google Scholar 

  • Tan X, Xu A, Zhao T, Zhao Q, Zhang J, Fan C, Deng Y, Freywald A, Genth H, Xiang J (2018) Simulated microgravity inhibits cell focal adhesions leading to reduced melanoma cell proliferation and metastasis via FAK/RhoA-regulated mTORC1 and AMPK pathways. Sci Rep 8:3769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang ZC, Liu H, Bai YG, Yu JW, Zhang HJ, Cheng YP, Bao JX, Ren XL, Ma HZ, Ma J (2015) 28-Day hindlimb unweighting reduces expression of Rho kinase and inhibits its effects in femoral artery of rat. J Physiol Biochem 71:205–216

    Article  CAS  PubMed  Google Scholar 

  • Yin M, Lu Q, Liu X, Wang T, Liu Y, Chen L (2016) Silencing Drp1 inhibits glioma cells proliferation and invasion by RHOA/ ROCK1 pathway. Biochem Biophys Res Commun 478:663–668

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Feng H, Li Z, Guo J, Li M (2018) Aspirin is involved in the cell cycle arrest, apoptosis, cell migration, and invasion of oral squamous cell carcinoma. Int J Mol Sci 19. https://doi.org/10.3390/ijms19072029

  • Zhao T, Tang X, Umeshappa CS, Ma H, Gao H, Deng Y, Freywald A, Xiang J (2016) Simulated microgravity promotes cell apoptosis through suppressing Uev1A/TICAM/TRAF/NF-kappaB-regulated anti-apoptosis and p53/PCNA- and ATM/ATR-Chk1/2-controlled DNA-damage response pathways. J Cell Biochem 117:2138–2148

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr. Austin Cape at ASJ Editors for careful reading and feedback.

Funding

The present study was supported by the Youth Science and Technology Innovation Personnel Training Project of Shaanxi Province (No. 2017KJXX-84), the National Natural Science Foundation of China (Nos. 81402055 and 81602494), and the Natural Science Foundation of Shaanxi Province (No. 2016JM8014).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Zucheng Han or Jun Chen.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Editor: Tetsuji Okamoto

Banglian Deng, Rongrong Liu, and Xin Tian are the co-first authors to this article and contribute equally to this research project.

Electronic supplementary material

ESM 1

(DOCX 211 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Deng, B., Liu, R., Tian, X. et al. Simulated microgravity inhibits the viability and migration of glioma via FAK/RhoA/Rock and FAK/Nek2 signaling. In Vitro Cell.Dev.Biol.-Animal 55, 260–271 (2019). https://doi.org/10.1007/s11626-019-00334-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-019-00334-7

Keywords

Navigation