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Prolonged exposure to simulated microgravity promotes stemness impairing morphological, metabolic and migratory profile of pancreatic cancer cells: a comprehensive proteomic, lipidomic and transcriptomic analysis

BACKGROUND: The impact of the absence of gravity on cancer cells is of great interest, especially today that space is more accessible than ever. Despite advances, few and contradictory data are available mainly due to different setup, experimental design and time point analyzed. METHODS: Exploiting...

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Autores principales: Masini, Maria Angela, Bonetto, Valentina, Manfredi, Marcello, Pastò, Anna, Barberis, Elettra, Timo, Sara, Vanella, Virginia Vita, Robotti, Elisa, Masetto, Francesca, Andreoli, Francesca, Fiore, Alessandra, Tavella, Sara, Sica, Antonio, Donadelli, Massimo, Marengo, Emilio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990939/
https://www.ncbi.nlm.nih.gov/pubmed/35391557
http://dx.doi.org/10.1007/s00018-022-04243-z
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author Masini, Maria Angela
Bonetto, Valentina
Manfredi, Marcello
Pastò, Anna
Barberis, Elettra
Timo, Sara
Vanella, Virginia Vita
Robotti, Elisa
Masetto, Francesca
Andreoli, Francesca
Fiore, Alessandra
Tavella, Sara
Sica, Antonio
Donadelli, Massimo
Marengo, Emilio
author_facet Masini, Maria Angela
Bonetto, Valentina
Manfredi, Marcello
Pastò, Anna
Barberis, Elettra
Timo, Sara
Vanella, Virginia Vita
Robotti, Elisa
Masetto, Francesca
Andreoli, Francesca
Fiore, Alessandra
Tavella, Sara
Sica, Antonio
Donadelli, Massimo
Marengo, Emilio
author_sort Masini, Maria Angela
collection PubMed
description BACKGROUND: The impact of the absence of gravity on cancer cells is of great interest, especially today that space is more accessible than ever. Despite advances, few and contradictory data are available mainly due to different setup, experimental design and time point analyzed. METHODS: Exploiting a Random Positioning Machine, we dissected the effects of long-term exposure to simulated microgravity (SMG) on pancreatic cancer cells performing proteomic, lipidomic and transcriptomic analysis at 1, 7 and 9 days. RESULTS: Our results indicated that SMG affects cellular morphology through a time-dependent activation of Actin-based motility via Rho and Cdc42 pathways leading to actin rearrangement, formation of 3D spheroids and enhancement of epithelial-to-mesenchymal transition. Bioinformatic analysis reveals that SMG may activates ERK5/NF-κB/IL-8 axis that triggers the expansion of cancer stem cells with an increased migratory capability. These cells, to remediate energy stress and apoptosis activation, undergo a metabolic reprogramming orchestrated by HIF-1α and PI3K/Akt pathways that upregulate glycolysis and impair β-oxidation, suggesting a de novo synthesis of triglycerides for the membrane lipid bilayer formation. CONCLUSIONS: SMG revolutionizes tumor cell behavior and metabolism leading to the acquisition of an aggressive and metastatic stem cell-like phenotype. These results dissect the time-dependent cellular alterations induced by SMG and pave the base for altered gravity conditions as new anti-cancer technology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-022-04243-z.
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spelling pubmed-89909392022-04-22 Prolonged exposure to simulated microgravity promotes stemness impairing morphological, metabolic and migratory profile of pancreatic cancer cells: a comprehensive proteomic, lipidomic and transcriptomic analysis Masini, Maria Angela Bonetto, Valentina Manfredi, Marcello Pastò, Anna Barberis, Elettra Timo, Sara Vanella, Virginia Vita Robotti, Elisa Masetto, Francesca Andreoli, Francesca Fiore, Alessandra Tavella, Sara Sica, Antonio Donadelli, Massimo Marengo, Emilio Cell Mol Life Sci Original Article BACKGROUND: The impact of the absence of gravity on cancer cells is of great interest, especially today that space is more accessible than ever. Despite advances, few and contradictory data are available mainly due to different setup, experimental design and time point analyzed. METHODS: Exploiting a Random Positioning Machine, we dissected the effects of long-term exposure to simulated microgravity (SMG) on pancreatic cancer cells performing proteomic, lipidomic and transcriptomic analysis at 1, 7 and 9 days. RESULTS: Our results indicated that SMG affects cellular morphology through a time-dependent activation of Actin-based motility via Rho and Cdc42 pathways leading to actin rearrangement, formation of 3D spheroids and enhancement of epithelial-to-mesenchymal transition. Bioinformatic analysis reveals that SMG may activates ERK5/NF-κB/IL-8 axis that triggers the expansion of cancer stem cells with an increased migratory capability. These cells, to remediate energy stress and apoptosis activation, undergo a metabolic reprogramming orchestrated by HIF-1α and PI3K/Akt pathways that upregulate glycolysis and impair β-oxidation, suggesting a de novo synthesis of triglycerides for the membrane lipid bilayer formation. CONCLUSIONS: SMG revolutionizes tumor cell behavior and metabolism leading to the acquisition of an aggressive and metastatic stem cell-like phenotype. These results dissect the time-dependent cellular alterations induced by SMG and pave the base for altered gravity conditions as new anti-cancer technology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-022-04243-z. Springer International Publishing 2022-04-07 2022 /pmc/articles/PMC8990939/ /pubmed/35391557 http://dx.doi.org/10.1007/s00018-022-04243-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Masini, Maria Angela
Bonetto, Valentina
Manfredi, Marcello
Pastò, Anna
Barberis, Elettra
Timo, Sara
Vanella, Virginia Vita
Robotti, Elisa
Masetto, Francesca
Andreoli, Francesca
Fiore, Alessandra
Tavella, Sara
Sica, Antonio
Donadelli, Massimo
Marengo, Emilio
Prolonged exposure to simulated microgravity promotes stemness impairing morphological, metabolic and migratory profile of pancreatic cancer cells: a comprehensive proteomic, lipidomic and transcriptomic analysis
title Prolonged exposure to simulated microgravity promotes stemness impairing morphological, metabolic and migratory profile of pancreatic cancer cells: a comprehensive proteomic, lipidomic and transcriptomic analysis
title_full Prolonged exposure to simulated microgravity promotes stemness impairing morphological, metabolic and migratory profile of pancreatic cancer cells: a comprehensive proteomic, lipidomic and transcriptomic analysis
title_fullStr Prolonged exposure to simulated microgravity promotes stemness impairing morphological, metabolic and migratory profile of pancreatic cancer cells: a comprehensive proteomic, lipidomic and transcriptomic analysis
title_full_unstemmed Prolonged exposure to simulated microgravity promotes stemness impairing morphological, metabolic and migratory profile of pancreatic cancer cells: a comprehensive proteomic, lipidomic and transcriptomic analysis
title_short Prolonged exposure to simulated microgravity promotes stemness impairing morphological, metabolic and migratory profile of pancreatic cancer cells: a comprehensive proteomic, lipidomic and transcriptomic analysis
title_sort prolonged exposure to simulated microgravity promotes stemness impairing morphological, metabolic and migratory profile of pancreatic cancer cells: a comprehensive proteomic, lipidomic and transcriptomic analysis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990939/
https://www.ncbi.nlm.nih.gov/pubmed/35391557
http://dx.doi.org/10.1007/s00018-022-04243-z
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