Extracellular superoxide dismutase regulates the expression of small gtpase regulatory proteins GEFs, GAPs, and GDI

PloS One
Mikko O LaukkanenMaria Domenica Castellone

Abstract

Extracellular superoxide dismutase (SOD3), which catalyzes the dismutation of superoxide anions to hydrogen peroxide at the cell membranes, regulates the cellular growth in a dose-dependent manner. This enzyme induces primary cell proliferation and immortalization at low expression levels whereas it activates cancer barrier signaling through the p53-p21 pathway at high expression levels, causing growth arrest, senescence, and apoptosis. Because previous reports suggested that the SOD3-induced reduction in the rates of cellular growth and migration also occurred in the absence of functional p53 signaling, in the current study we investigated the SOD3-induced growth-suppressive mechanisms in anaplastic thyroid cancer cells. Based on our data, the robust over-expression of SOD3 increased the level of phosphorylation of the EGFR, ERBB2, RYK, ALK, FLT3, and EPHA10 receptor tyrosine kinases with the consequent downstream activation of the SRC, FYN, YES, HCK, and LYN kinases. However, pull-down experiments focusing on the small GTPase RAS, RAC, CDC42, and RHO revealed a reduced level of growth and migration signal transduction, such as the lack of stimulation of the mitogen pathway, in the SOD3 over-expressing cells, which was confirm...Continue Reading

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Citations

Dec 15, 2015·Cancer Cell International·Francesca CammarotaMikko O Laukkanen
Nov 10, 2015·BioMed Research International·Francesca CammarotaMikko O Laukkanen
Jun 14, 2016·Oxidative Medicine and Cellular Longevity·Mikko O Laukkanen
Dec 7, 2016·European Journal of Cell Biology·Boris CastilloLou W Kim
Oct 20, 2017·Cancer Medicine·Adel Rezaei MoghadamFaris Farassati
Sep 13, 2018·Journal of Cellular Biochemistry·G R C PereiraJ F De Mesquita
Feb 10, 2018·Nature Communications·Emilia MiraSantos Mañes
Jul 1, 2020·Antioxidants & Redox Signaling·Raffaella Bonavita, Mikko O Laukkanen
May 21, 2020·Frontiers in Genetics·Mingwei ZhangJinsheng Hong
Feb 7, 2021·Medical Hypotheses·Sandra Caramujo-BalseiroLina Carvalho

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Methods Mentioned

BETA
GTPase
transfection
pull-down
fluorescence microscopy
PCR
protein array
nucleotide exchange
GTPases
nucleotide dissociation

Software Mentioned

GSEA
biomaRt
Bioconductor6
ImageJ
R
GEL blot
BeadStudio

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