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Circulating Tumor Cell Migration Requires Fibronectin Acting through Integrin B1 or SLUG

Fibronectin (FN1) is an extracellular matrix protein gaining increasing attention for its multifaceted roles in cancer progression. Using our recently established circulating tumor cell (CTC) lines, we had demonstrated increased FN1 expression and enhanced migration in CTC lines, in comparison to pr...

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Detalles Bibliográficos
Autores principales: Huaman, Jeannette, Ogunwobi, Olorunseun O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408126/
https://www.ncbi.nlm.nih.gov/pubmed/32630254
http://dx.doi.org/10.3390/cells9071594
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author Huaman, Jeannette
Ogunwobi, Olorunseun O.
author_facet Huaman, Jeannette
Ogunwobi, Olorunseun O.
author_sort Huaman, Jeannette
collection PubMed
description Fibronectin (FN1) is an extracellular matrix protein gaining increasing attention for its multifaceted roles in cancer progression. Using our recently established circulating tumor cell (CTC) lines, we had demonstrated increased FN1 expression and enhanced migration in CTC lines, in comparison to primary tumor cell lines. Whether increased FN1 expression is directly required for CTC migration, and the specific role of FN1’s regulation of integrin B1 (ITGB1) and SLUG (SNAI2) in CTC migration remains unclear. Here, for the first time, we report that the knockdown of FN1, ITGB1, or SLUG expression in CTCs leads to a significant decrease in CTC migration. Knocking down two or all three of these proteins simultaneously did not further inhibit migration. We observed a corresponding increase in CTC migration when recombinant FN1 was added to CTCs. This effect was significantly impeded by prior knockdown of ITGB1 or SLUG. Using knock down experiments and western blotting analysis, we confirmed FN1’s regulation of ITGB1 and SLUG to occur via two separate, independent pathways. Consequently, we can conclude that FN1-dependent enhanced migration of CTCs requires downstream signaling through either ITGB1 or SLUG and that FN1 regulation of ITGB1 and SLUG may have important implications for cancer progression and metastasis.
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spelling pubmed-74081262020-08-25 Circulating Tumor Cell Migration Requires Fibronectin Acting through Integrin B1 or SLUG Huaman, Jeannette Ogunwobi, Olorunseun O. Cells Article Fibronectin (FN1) is an extracellular matrix protein gaining increasing attention for its multifaceted roles in cancer progression. Using our recently established circulating tumor cell (CTC) lines, we had demonstrated increased FN1 expression and enhanced migration in CTC lines, in comparison to primary tumor cell lines. Whether increased FN1 expression is directly required for CTC migration, and the specific role of FN1’s regulation of integrin B1 (ITGB1) and SLUG (SNAI2) in CTC migration remains unclear. Here, for the first time, we report that the knockdown of FN1, ITGB1, or SLUG expression in CTCs leads to a significant decrease in CTC migration. Knocking down two or all three of these proteins simultaneously did not further inhibit migration. We observed a corresponding increase in CTC migration when recombinant FN1 was added to CTCs. This effect was significantly impeded by prior knockdown of ITGB1 or SLUG. Using knock down experiments and western blotting analysis, we confirmed FN1’s regulation of ITGB1 and SLUG to occur via two separate, independent pathways. Consequently, we can conclude that FN1-dependent enhanced migration of CTCs requires downstream signaling through either ITGB1 or SLUG and that FN1 regulation of ITGB1 and SLUG may have important implications for cancer progression and metastasis. MDPI 2020-07-01 /pmc/articles/PMC7408126/ /pubmed/32630254 http://dx.doi.org/10.3390/cells9071594 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huaman, Jeannette
Ogunwobi, Olorunseun O.
Circulating Tumor Cell Migration Requires Fibronectin Acting through Integrin B1 or SLUG
title Circulating Tumor Cell Migration Requires Fibronectin Acting through Integrin B1 or SLUG
title_full Circulating Tumor Cell Migration Requires Fibronectin Acting through Integrin B1 or SLUG
title_fullStr Circulating Tumor Cell Migration Requires Fibronectin Acting through Integrin B1 or SLUG
title_full_unstemmed Circulating Tumor Cell Migration Requires Fibronectin Acting through Integrin B1 or SLUG
title_short Circulating Tumor Cell Migration Requires Fibronectin Acting through Integrin B1 or SLUG
title_sort circulating tumor cell migration requires fibronectin acting through integrin b1 or slug
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408126/
https://www.ncbi.nlm.nih.gov/pubmed/32630254
http://dx.doi.org/10.3390/cells9071594
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