Cargando…
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...
Autores principales: | , |
---|---|
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 |
_version_ | 1783567765761687552 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7408126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT huamanjeannette circulatingtumorcellmigrationrequiresfibronectinactingthroughintegrinb1orslug AT ogunwobiolorunseuno circulatingtumorcellmigrationrequiresfibronectinactingthroughintegrinb1orslug |