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Direct evidence for cell adhesion-mediated radioresistance (CAM-RR) on the level of individual integrin β1 clusters.

Babel, Laura ; Grunewald, Miriam ; Lehn, Robert ; Langhans, Markus ; Meckel, Tobias (2017)
Direct evidence for cell adhesion-mediated radioresistance (CAM-RR) on the level of individual integrin β1 clusters.
In: Scientific reports, 7 (1)
Artikel, Bibliographie

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Kurzbeschreibung (Abstract)

The cellular interaction with the extracellular matrix (ECM) modulates many key processes such as proliferation, migration, differentiation and survival. In addition, cells cultured under 3D conditions in presence of an ECM display a marked radioresistance towards ionizing radiation (IR) in comparison to conventionally 2D cultured cells. This process, also known as "cell-adhesion-mediated-radio-resistance" (CAM-RR), has been linked to the chromatin structure that differs between cells cultured on stiff surfaces versus cell grown on soft planar supports or in 3D environments. As integrins are the key mediators of cell adhesion and mechanosensing, they originate the molecular signalling towards chromatin remodelling in response to a cell's microenvironment. We aimed to investigate this molecular origin that leads to CAM-RR by investigating the distribution of integrins at the single molecule level and show that cells cultured in 2D keep a lower fraction of integrin β1 in clusters and maintain a less defined cluster status than 3D cultured cells. Upon X-irradiation this nanoscale distribution of integrin β1 is disturbed at much lower dosages in 2D versus 3D cultured cells. Radioresistance is thus linked to the ability to maintain a well defined organization of integrins in clusters, making integrin distribution a potential drug target for radiosensitization.

Typ des Eintrags: Artikel
Erschienen: 2017
Autor(en): Babel, Laura ; Grunewald, Miriam ; Lehn, Robert ; Langhans, Markus ; Meckel, Tobias
Art des Eintrags: Bibliographie
Titel: Direct evidence for cell adhesion-mediated radioresistance (CAM-RR) on the level of individual integrin β1 clusters.
Sprache: Englisch
Publikationsjahr: 13 Juni 2017
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Scientific reports
Jahrgang/Volume einer Zeitschrift: 7
(Heft-)Nummer: 1
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Kurzbeschreibung (Abstract):

The cellular interaction with the extracellular matrix (ECM) modulates many key processes such as proliferation, migration, differentiation and survival. In addition, cells cultured under 3D conditions in presence of an ECM display a marked radioresistance towards ionizing radiation (IR) in comparison to conventionally 2D cultured cells. This process, also known as "cell-adhesion-mediated-radio-resistance" (CAM-RR), has been linked to the chromatin structure that differs between cells cultured on stiff surfaces versus cell grown on soft planar supports or in 3D environments. As integrins are the key mediators of cell adhesion and mechanosensing, they originate the molecular signalling towards chromatin remodelling in response to a cell's microenvironment. We aimed to investigate this molecular origin that leads to CAM-RR by investigating the distribution of integrins at the single molecule level and show that cells cultured in 2D keep a lower fraction of integrin β1 in clusters and maintain a less defined cluster status than 3D cultured cells. Upon X-irradiation this nanoscale distribution of integrin β1 is disturbed at much lower dosages in 2D versus 3D cultured cells. Radioresistance is thus linked to the ability to maintain a well defined organization of integrins in clusters, making integrin distribution a potential drug target for radiosensitization.

ID-Nummer: pmid:28611417
Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
10 Fachbereich Biologie > Membrane Dynamics
Hinterlegungsdatum: 20 Jun 2017 06:38
Letzte Änderung: 03 Jul 2024 02:27
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