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Induction, regulation and roles of neural adhesion molecule L1CAM in cellular senescence

Aging involves tissue accumulation of senescent cells (SC) whose elimination through senolytic approaches may evoke organismal rejuvenation. SC also contribute to aging-associated pathologies including cancer, hence it is imperative to better identify and target SC. Here, we aimed to identify new ce...

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Autores principales: Mrazkova, Blanka, Dzijak, Rastislav, Imrichova, Terezie, Kyjacova, Lenka, Barath, Peter, Dzubak, Petr, Holub, Dusan, Hajduch, Marian, Nahacka, Zuzana, Andera, Ladislav, Holicek, Petr, Vasicova, Pavla, Sapega, Olena, Bartek, Jiri, Hodny, Zdenek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892697/
https://www.ncbi.nlm.nih.gov/pubmed/29615539
http://dx.doi.org/10.18632/aging.101404
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author Mrazkova, Blanka
Dzijak, Rastislav
Imrichova, Terezie
Kyjacova, Lenka
Barath, Peter
Dzubak, Petr
Holub, Dusan
Hajduch, Marian
Nahacka, Zuzana
Andera, Ladislav
Holicek, Petr
Vasicova, Pavla
Sapega, Olena
Bartek, Jiri
Hodny, Zdenek
author_facet Mrazkova, Blanka
Dzijak, Rastislav
Imrichova, Terezie
Kyjacova, Lenka
Barath, Peter
Dzubak, Petr
Holub, Dusan
Hajduch, Marian
Nahacka, Zuzana
Andera, Ladislav
Holicek, Petr
Vasicova, Pavla
Sapega, Olena
Bartek, Jiri
Hodny, Zdenek
author_sort Mrazkova, Blanka
collection PubMed
description Aging involves tissue accumulation of senescent cells (SC) whose elimination through senolytic approaches may evoke organismal rejuvenation. SC also contribute to aging-associated pathologies including cancer, hence it is imperative to better identify and target SC. Here, we aimed to identify new cell-surface proteins differentially expressed on human SC. Besides previously reported proteins enriched on SC, we identified 78 proteins enriched and 73 proteins underrepresented in replicatively senescent BJ fibroblasts, including L1CAM, whose expression is normally restricted to the neural system and kidneys. L1CAM was: 1) induced in premature forms of cellular senescence triggered chemically and by gamma-radiation, but not in Ras-induced senescence; 2) induced upon inhibition of cyclin-dependent kinases by p16(INK4a); 3) induced by TGFbeta and suppressed by RAS/MAPK(Erk) signaling (the latter explaining the lack of L1CAM induction in RAS-induced senescence); and 4) induced upon downregulation of growth-associated gene ANT2, growth in low-glucose medium or inhibition of the mevalonate pathway. These data indicate that L1CAM is controlled by a number of cell growth- and metabolism-related pathways during SC development. Functionally, SC with enhanced surface L1CAM showed increased adhesion to extracellular matrix and migrated faster. Our results provide mechanistic insights into senescence of human cells, with implications for future senolytic strategies.
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spelling pubmed-58926972018-04-13 Induction, regulation and roles of neural adhesion molecule L1CAM in cellular senescence Mrazkova, Blanka Dzijak, Rastislav Imrichova, Terezie Kyjacova, Lenka Barath, Peter Dzubak, Petr Holub, Dusan Hajduch, Marian Nahacka, Zuzana Andera, Ladislav Holicek, Petr Vasicova, Pavla Sapega, Olena Bartek, Jiri Hodny, Zdenek Aging (Albany NY) Research Paper Aging involves tissue accumulation of senescent cells (SC) whose elimination through senolytic approaches may evoke organismal rejuvenation. SC also contribute to aging-associated pathologies including cancer, hence it is imperative to better identify and target SC. Here, we aimed to identify new cell-surface proteins differentially expressed on human SC. Besides previously reported proteins enriched on SC, we identified 78 proteins enriched and 73 proteins underrepresented in replicatively senescent BJ fibroblasts, including L1CAM, whose expression is normally restricted to the neural system and kidneys. L1CAM was: 1) induced in premature forms of cellular senescence triggered chemically and by gamma-radiation, but not in Ras-induced senescence; 2) induced upon inhibition of cyclin-dependent kinases by p16(INK4a); 3) induced by TGFbeta and suppressed by RAS/MAPK(Erk) signaling (the latter explaining the lack of L1CAM induction in RAS-induced senescence); and 4) induced upon downregulation of growth-associated gene ANT2, growth in low-glucose medium or inhibition of the mevalonate pathway. These data indicate that L1CAM is controlled by a number of cell growth- and metabolism-related pathways during SC development. Functionally, SC with enhanced surface L1CAM showed increased adhesion to extracellular matrix and migrated faster. Our results provide mechanistic insights into senescence of human cells, with implications for future senolytic strategies. Impact Journals 2018-03-28 /pmc/articles/PMC5892697/ /pubmed/29615539 http://dx.doi.org/10.18632/aging.101404 Text en Copyright © 2018 Mrazhkova et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Mrazkova, Blanka
Dzijak, Rastislav
Imrichova, Terezie
Kyjacova, Lenka
Barath, Peter
Dzubak, Petr
Holub, Dusan
Hajduch, Marian
Nahacka, Zuzana
Andera, Ladislav
Holicek, Petr
Vasicova, Pavla
Sapega, Olena
Bartek, Jiri
Hodny, Zdenek
Induction, regulation and roles of neural adhesion molecule L1CAM in cellular senescence
title Induction, regulation and roles of neural adhesion molecule L1CAM in cellular senescence
title_full Induction, regulation and roles of neural adhesion molecule L1CAM in cellular senescence
title_fullStr Induction, regulation and roles of neural adhesion molecule L1CAM in cellular senescence
title_full_unstemmed Induction, regulation and roles of neural adhesion molecule L1CAM in cellular senescence
title_short Induction, regulation and roles of neural adhesion molecule L1CAM in cellular senescence
title_sort induction, regulation and roles of neural adhesion molecule l1cam in cellular senescence
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892697/
https://www.ncbi.nlm.nih.gov/pubmed/29615539
http://dx.doi.org/10.18632/aging.101404
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