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Single live cell TGF-β signalling imaging: breast cancer cell motility and migration is driven by sub-populations of cells with dynamic TGF-β-Smad3 activity

BACKGROUND: Metastasis is a process where only a small subset of cells is capable of successfully migrating to and propagating at secondary sites. TGF-β signalling is widely known for its role in cancer metastasis and is associated with cell migration in whole cell populations. FINDINGS: We extend t...

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Autores principales: Luwor, Rodney B, Hakmana, Dulani, Iaria, Josephine, Nheu, Thao V, Simpson, Richard J, Zhu, Hong-Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343191/
https://www.ncbi.nlm.nih.gov/pubmed/25744371
http://dx.doi.org/10.1186/s12943-015-0309-1
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author Luwor, Rodney B
Hakmana, Dulani
Iaria, Josephine
Nheu, Thao V
Simpson, Richard J
Zhu, Hong-Jian
author_facet Luwor, Rodney B
Hakmana, Dulani
Iaria, Josephine
Nheu, Thao V
Simpson, Richard J
Zhu, Hong-Jian
author_sort Luwor, Rodney B
collection PubMed
description BACKGROUND: Metastasis is a process where only a small subset of cells is capable of successfully migrating to and propagating at secondary sites. TGF-β signalling is widely known for its role in cancer metastasis and is associated with cell migration in whole cell populations. FINDINGS: We extend these findings by investigating the role of TGF-β signalling in promoting migration and motility by imaging the signalling activity in live, individual MDA-MB-231 cancer cells utilizing a novel Smad3 Td-Tomato reporter adenovirus. Here we find that not all MDA-MB-231 cancer cells have similar TGF-β mediated Smad3 transcription activity and display at least two distinct migratory populations. Importantly, Smad3 activity was significantly higher within migratory cells compared to non-migrated cells in wound healing and transwell assays. Furthermore, time-lapse experiments showed that MDA-MB-231 cells displaying Smad3 activity moved faster and a greater distance compared to cells not displaying Smad3 reporter activity. Interestingly, despite being more motile than cells with undetectable levels of Smad3 activity, high Smad3 activity was detrimental to cell motility compared to low and medium level of Smad3 activity. CONCLUSIONS: We have developed a method enabling real-time visualization of TGF-β signalling in single live cells. Breast cancer cell motility and migration is driven by sub-populations of cells with dynamic TGF-β-Smad3 activity. Those sub-populations may be responsible for tumor invasion and metastasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-015-0309-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-43431912015-02-28 Single live cell TGF-β signalling imaging: breast cancer cell motility and migration is driven by sub-populations of cells with dynamic TGF-β-Smad3 activity Luwor, Rodney B Hakmana, Dulani Iaria, Josephine Nheu, Thao V Simpson, Richard J Zhu, Hong-Jian Mol Cancer Research BACKGROUND: Metastasis is a process where only a small subset of cells is capable of successfully migrating to and propagating at secondary sites. TGF-β signalling is widely known for its role in cancer metastasis and is associated with cell migration in whole cell populations. FINDINGS: We extend these findings by investigating the role of TGF-β signalling in promoting migration and motility by imaging the signalling activity in live, individual MDA-MB-231 cancer cells utilizing a novel Smad3 Td-Tomato reporter adenovirus. Here we find that not all MDA-MB-231 cancer cells have similar TGF-β mediated Smad3 transcription activity and display at least two distinct migratory populations. Importantly, Smad3 activity was significantly higher within migratory cells compared to non-migrated cells in wound healing and transwell assays. Furthermore, time-lapse experiments showed that MDA-MB-231 cells displaying Smad3 activity moved faster and a greater distance compared to cells not displaying Smad3 reporter activity. Interestingly, despite being more motile than cells with undetectable levels of Smad3 activity, high Smad3 activity was detrimental to cell motility compared to low and medium level of Smad3 activity. CONCLUSIONS: We have developed a method enabling real-time visualization of TGF-β signalling in single live cells. Breast cancer cell motility and migration is driven by sub-populations of cells with dynamic TGF-β-Smad3 activity. Those sub-populations may be responsible for tumor invasion and metastasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-015-0309-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-02-22 /pmc/articles/PMC4343191/ /pubmed/25744371 http://dx.doi.org/10.1186/s12943-015-0309-1 Text en © Luwor et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Luwor, Rodney B
Hakmana, Dulani
Iaria, Josephine
Nheu, Thao V
Simpson, Richard J
Zhu, Hong-Jian
Single live cell TGF-β signalling imaging: breast cancer cell motility and migration is driven by sub-populations of cells with dynamic TGF-β-Smad3 activity
title Single live cell TGF-β signalling imaging: breast cancer cell motility and migration is driven by sub-populations of cells with dynamic TGF-β-Smad3 activity
title_full Single live cell TGF-β signalling imaging: breast cancer cell motility and migration is driven by sub-populations of cells with dynamic TGF-β-Smad3 activity
title_fullStr Single live cell TGF-β signalling imaging: breast cancer cell motility and migration is driven by sub-populations of cells with dynamic TGF-β-Smad3 activity
title_full_unstemmed Single live cell TGF-β signalling imaging: breast cancer cell motility and migration is driven by sub-populations of cells with dynamic TGF-β-Smad3 activity
title_short Single live cell TGF-β signalling imaging: breast cancer cell motility and migration is driven by sub-populations of cells with dynamic TGF-β-Smad3 activity
title_sort single live cell tgf-β signalling imaging: breast cancer cell motility and migration is driven by sub-populations of cells with dynamic tgf-β-smad3 activity
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343191/
https://www.ncbi.nlm.nih.gov/pubmed/25744371
http://dx.doi.org/10.1186/s12943-015-0309-1
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