Aarhus Universitet

Jayashree Sahana

Decreased E-Cadherin in MCF7 Human Breast Cancer Cells Forming Multicellular Spheroids Exposed to Simulated Microgravity

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DOI

  • Jayashree Sahana
  • Mohamed Zakaria Nassef, Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von Guericke-University, Magdeburg, Germany.
  • ,
  • Markus Wehland, Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von Guericke-University, Magdeburg, Germany.
  • ,
  • Sascha Kopp, Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von Guericke-University, Magdeburg, Germany.
  • ,
  • Marcus Krüger, Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von Guericke-University, Magdeburg, Germany.
  • ,
  • Thomas J Corydon
  • Manfred Infanger, Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von Guericke-University, Magdeburg, Germany.
  • ,
  • Johann Bauer, Max-Planck Institute for Biochemistry, Martinsried, Germany.
  • ,
  • Daniela Grimm

MCF7 human breast cancer cells were cultured under normal gravity (1g) and on a random positioning machine (RPM) preventing sedimentation. After two weeks, adherent 1g-control and adherent RPM cells (AD) as well as multicellular spheroids (MCS) were harvested. AD and MCS had been exposed to the RPM in the same culture flask. In a subsequent proteome analysis, the majority of the proteins detected showed similar label-free quantification scores (LFQ) in each of the respective subpopulations, but in both AD or MCS cultures, proteins were also found whose LFQs deviated at least twofold from their counterparts in the 1g-control cells. They included the cell junction protein E-cadherin, which was diminished in MCS cells, where proteins of the E-cadherin autodegradation pathway were enhanced and the c-Src (Proto-oncogene tyrosine-protein kinase c-Src) was detected. Spheroid formation was prevented by inhibition of c-Src but promoted by antibodies blocking E-cadherin activity. An interaction analysis of the detected proteins that are involved in forming and regulating junctions or adhesion complexes and in E-cadherin autodegradation indicated connections between the two protein groups. This suggests that the balance of proteins that up- or down-regulate E-cadherin mediates the tendency of MCF7 cells to form MCS during RPM-exposure. This article is protected by copyright. All rights reserved.

OriginalsprogEngelsk
Artikelnummer1800015
TidsskriftProteomics
Vol/bind18
Nummer13
Antal sider10
ISSN1615-9853
DOI
StatusUdgivet - jul. 2018

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