Simulated microgravity inhibits cell focal adhesions leading to reduced melanoma cell proliferation and metastasis via FAK/RhoA-regulated mTORC1 and AMPK pathways

Scientific Reports
Xin TanJim Xiang

Abstract

Simulated microgravity (SMG) was reported to affect tumor cell proliferation and metastasis. However, the underlying mechanism is elusive. In this study, we demonstrate that clinostat-modelled SMG reduces BL6-10 melanoma cell proliferation, adhesion and invasiveness in vitro and decreases tumor lung metastasis in vivo. It down-regulates metastasis-related integrin α6β4, MMP9 and Met72 molecules. SMG significantly reduces formation of focal adhesions and activation of focal adhesion kinase (FAK) and Rho family proteins (RhoA, Rac1 and Cdc42) and of mTORC1 kinase, but activates AMPK and ULK1 kinases. We demonstrate that SMG inhibits NADH induction and glycolysis, but induces mitochondrial biogenesis. Interestingly, administration of a RhoA activator, the cytotoxic necrotizing factor-1 (CNF1) effectively converts SMG-triggered alterations and effects on mitochondria biogenesis or glycolysis. CNF1 also converts the SMG-altered cell proliferation and tumor metastasis. In contrast, mTORC inhibitor, rapamycin, produces opposite responses and mimics SMG-induced effects in cells at normal gravity. Taken together, our observations indicate that SMG inhibits focal adhesions, leading to inhibition of signaling FAK and RhoA, and the mTORC1 ...Continue Reading

References

Apr 1, 1994·Current Biology : CB·J M CortonD G Hardie
Feb 7, 1998·Science·A Hall
Apr 9, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J VassyD Schoevaert
Mar 5, 2003·The Journal of Cell Biology·Datsun A HsiaDavid D Schlaepfer
Mar 9, 2004·Advances in Space Research : the Official Journal of the Committee on Space Research (COSPAR)·M Hughes-Fulford
Mar 9, 2004·Advances in Space Research : the Official Journal of the Committee on Space Research (COSPAR)·J VassyD Schoevaert
Oct 16, 2008·The Journal of Biological Chemistry·Dominic P Del ReJoan Heller Brown
Jan 27, 2009·Cancer Metastasis Reviews·Jihe Zhao, Jun-Lin Guan
Feb 7, 2009·Nature Reviews. Molecular Cell Biology·Benjamin GeigerAlexander D Bershadsky
Dec 24, 2009·Nature Reviews. Cancer·Jay S Desgrosellier, David A Cheresh
Jul 1, 2010·Journal of Bone and Mineral Metabolism·Ritu SaxenaJay M McDonald
Jan 25, 2011·Nature Cell Biology·Joungmok KimKun-Liang Guan
Aug 24, 2011·The Journal of Cell Biology·Bill Wickstead, Keith Gull
Sep 6, 2011·Nature Cell Biology·Maria M Mihaylova, Reuben J Shaw
Jan 5, 2012·PloS One·Yulan WangHaiying Hang
Feb 22, 2012·Trends in Immunology·Valerie A Gerriets, Jeffrey C Rathmell
Mar 23, 2012·Nature Reviews. Molecular Cell Biology·D Grahame HardieSimon A Hawley
Apr 21, 2012·Nature Reviews. Immunology·Hongbo Chi
Feb 14, 2013·In Vitro Cellular & Developmental Biology. Animal·De ChangChangting Liu
Aug 27, 2013·Immunity·Yuting MaGuido Kroemer
Jan 28, 2014·Bone·Yuvaraj SambandamSakamuri V Reddy
Aug 8, 2014·Nature Reviews. Cancer·Florian J SulzmaierDavid D Schlaepfer
Oct 16, 2014·Pharmacology & Therapeutics·Brian Y LeeRoger J Daly
Jan 5, 2016·Archivum Immunologiae Et Therapiae Experimentalis·Lei WeiJianjian Shi
Apr 14, 2016·International Journal of Molecular Sciences·Yeong-Min YooHan Sung Kim
Aug 19, 2016·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Timur MirzoevBoris Shenkman

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Citations

Mar 2, 2019·In Vitro Cellular & Developmental Biology. Animal·Banglian DengJun Chen
Jul 3, 2019·International Journal of Molecular Sciences·Mohamed Zakaria NassefDaniela Grimm
Apr 30, 2020·International Journal of Molecular Sciences·Xiao LinAirong Qian
Sep 19, 2020·International Journal of Molecular Sciences·Srujana NeelamYe Zhang
May 30, 2019·International Journal of Molecular Sciences·Marcus KrügerDaniela Grimm
Mar 8, 2020·International Journal of Molecular Sciences·Thomas J BauerDaniela Grimm
Nov 25, 2018·International Journal of Molecular Sciences·Maria Moreno-VillanuevaHonglu Wu
Mar 11, 2020·Frontiers in Cell and Developmental Biology·Peta BradburyJoshua Chou
Jan 11, 2020·Frontiers in Oncology·Wei MuMargot Zöller
Feb 13, 2020·International Journal of Molecular Sciences·Krassimira Ivanova, Ruth Hemmersbach
Jan 23, 2020·The Journal of Nutrition·Min Zhu, Xiu-Qi Wang
Jul 3, 2021·International Journal of Molecular Sciences·Ryosuke OzasaTakayoshi Nakano
Jul 20, 2021·Frontiers in Cell and Developmental Biology·Jayashree SahanaDaniela Grimm

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Methods Mentioned

BETA
GTPases
Assay
flow cytometry
fluorescence microscopy
light microscopy
GTPase
confocal microscopy
flow

Software Mentioned

Graphpad Prism -

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