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RASSF1C oncogene elicits amoeboid invasion, cancer stemness, and extracellular vesicle release via a SRC/Rho axis

Cell plasticity is a crucial hallmark leading to cancer metastasis. Upregulation of Rho/ROCK pathway drives actomyosin contractility, protrusive forces, and contributes to the occurrence of highly invasive amoeboid cells in tumors. Cancer stem cells are similarly associated with metastasis, but how...

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Autores principales: Tognoli, Maria Laura, Vlahov, Nikola, Steenbeek, Sander, Grawenda, Anna M, Eyres, Michael, Cano‐Rodriguez, David, Scrace, Simon, Kartsonaki, Christiana, von Kriegsheim, Alex, Willms, Eduard, Wood, Matthew J, Rots, Marianne G, van Rheenen, Jacco, O'Neill, Eric, Pankova, Daniela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521318/
https://www.ncbi.nlm.nih.gov/pubmed/34532864
http://dx.doi.org/10.15252/embj.2021107680
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author Tognoli, Maria Laura
Vlahov, Nikola
Steenbeek, Sander
Grawenda, Anna M
Eyres, Michael
Cano‐Rodriguez, David
Scrace, Simon
Kartsonaki, Christiana
von Kriegsheim, Alex
Willms, Eduard
Wood, Matthew J
Rots, Marianne G
van Rheenen, Jacco
O'Neill, Eric
Pankova, Daniela
author_facet Tognoli, Maria Laura
Vlahov, Nikola
Steenbeek, Sander
Grawenda, Anna M
Eyres, Michael
Cano‐Rodriguez, David
Scrace, Simon
Kartsonaki, Christiana
von Kriegsheim, Alex
Willms, Eduard
Wood, Matthew J
Rots, Marianne G
van Rheenen, Jacco
O'Neill, Eric
Pankova, Daniela
author_sort Tognoli, Maria Laura
collection PubMed
description Cell plasticity is a crucial hallmark leading to cancer metastasis. Upregulation of Rho/ROCK pathway drives actomyosin contractility, protrusive forces, and contributes to the occurrence of highly invasive amoeboid cells in tumors. Cancer stem cells are similarly associated with metastasis, but how these populations arise in tumors is not fully understood. Here, we show that the novel oncogene RASSF1C drives mesenchymal‐to‐amoeboid transition and stem cell attributes in breast cancer cells. Mechanistically, RASSF1C activates Rho/ROCK via SRC‐mediated RhoGDI inhibition, resulting in generation of actomyosin contractility. Moreover, we demonstrate that RASSF1C‐induced amoeboid cells display increased expression of cancer stem‐like markers such as CD133, ALDH1, and Nanog, and are accompanied by higher invasive potential in vitro and in vivo. Further, RASSF1C‐induced amoeboid cells employ extracellular vesicles to transfer the invasive phenotype to target cells and tissue. Importantly, the underlying RASSF1C‐driven biological processes concur to explain clinical data: namely, methylation of the RASSF1C promoter correlates with better survival in early‐stage breast cancer patients. Therefore, we propose the use of RASSF1 gene promoter methylation status as a biomarker for patient stratification.
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spelling pubmed-85213182021-10-29 RASSF1C oncogene elicits amoeboid invasion, cancer stemness, and extracellular vesicle release via a SRC/Rho axis Tognoli, Maria Laura Vlahov, Nikola Steenbeek, Sander Grawenda, Anna M Eyres, Michael Cano‐Rodriguez, David Scrace, Simon Kartsonaki, Christiana von Kriegsheim, Alex Willms, Eduard Wood, Matthew J Rots, Marianne G van Rheenen, Jacco O'Neill, Eric Pankova, Daniela EMBO J Articles Cell plasticity is a crucial hallmark leading to cancer metastasis. Upregulation of Rho/ROCK pathway drives actomyosin contractility, protrusive forces, and contributes to the occurrence of highly invasive amoeboid cells in tumors. Cancer stem cells are similarly associated with metastasis, but how these populations arise in tumors is not fully understood. Here, we show that the novel oncogene RASSF1C drives mesenchymal‐to‐amoeboid transition and stem cell attributes in breast cancer cells. Mechanistically, RASSF1C activates Rho/ROCK via SRC‐mediated RhoGDI inhibition, resulting in generation of actomyosin contractility. Moreover, we demonstrate that RASSF1C‐induced amoeboid cells display increased expression of cancer stem‐like markers such as CD133, ALDH1, and Nanog, and are accompanied by higher invasive potential in vitro and in vivo. Further, RASSF1C‐induced amoeboid cells employ extracellular vesicles to transfer the invasive phenotype to target cells and tissue. Importantly, the underlying RASSF1C‐driven biological processes concur to explain clinical data: namely, methylation of the RASSF1C promoter correlates with better survival in early‐stage breast cancer patients. Therefore, we propose the use of RASSF1 gene promoter methylation status as a biomarker for patient stratification. John Wiley and Sons Inc. 2021-09-17 2021-10-18 /pmc/articles/PMC8521318/ /pubmed/34532864 http://dx.doi.org/10.15252/embj.2021107680 Text en ©2021 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Tognoli, Maria Laura
Vlahov, Nikola
Steenbeek, Sander
Grawenda, Anna M
Eyres, Michael
Cano‐Rodriguez, David
Scrace, Simon
Kartsonaki, Christiana
von Kriegsheim, Alex
Willms, Eduard
Wood, Matthew J
Rots, Marianne G
van Rheenen, Jacco
O'Neill, Eric
Pankova, Daniela
RASSF1C oncogene elicits amoeboid invasion, cancer stemness, and extracellular vesicle release via a SRC/Rho axis
title RASSF1C oncogene elicits amoeboid invasion, cancer stemness, and extracellular vesicle release via a SRC/Rho axis
title_full RASSF1C oncogene elicits amoeboid invasion, cancer stemness, and extracellular vesicle release via a SRC/Rho axis
title_fullStr RASSF1C oncogene elicits amoeboid invasion, cancer stemness, and extracellular vesicle release via a SRC/Rho axis
title_full_unstemmed RASSF1C oncogene elicits amoeboid invasion, cancer stemness, and extracellular vesicle release via a SRC/Rho axis
title_short RASSF1C oncogene elicits amoeboid invasion, cancer stemness, and extracellular vesicle release via a SRC/Rho axis
title_sort rassf1c oncogene elicits amoeboid invasion, cancer stemness, and extracellular vesicle release via a src/rho axis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521318/
https://www.ncbi.nlm.nih.gov/pubmed/34532864
http://dx.doi.org/10.15252/embj.2021107680
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