Hypoxia, Snail and incomplete epithelial-mesenchymal transition in breast cancer.
(2009) In British Journal of Cancer 101. p.1769-1781- Abstract
- Background:Hypoxia is an element of the tumour microenvironment that impacts upon numerous cellular factors linked to clinical aggressiveness in cancer. One such factor, Snail, a master regulator of the epithelial-mesenchymal transition (EMT), has been implicated in key tumour biological processes such as invasion and metastasis. In this study we set out to investigate regulation of EMT in hypoxia, and the importance of Snail in cell migration and clinical outcome in breast cancer.Methods:Four breast cancer cell lines were exposed to 0.1% oxygen and expression of EMT markers was monitored. The migratory ability was analysed following Snail overexpression and silencing. Snail expression was assessed in 500 tumour samples from premenopausal... (More)
- Background:Hypoxia is an element of the tumour microenvironment that impacts upon numerous cellular factors linked to clinical aggressiveness in cancer. One such factor, Snail, a master regulator of the epithelial-mesenchymal transition (EMT), has been implicated in key tumour biological processes such as invasion and metastasis. In this study we set out to investigate regulation of EMT in hypoxia, and the importance of Snail in cell migration and clinical outcome in breast cancer.Methods:Four breast cancer cell lines were exposed to 0.1% oxygen and expression of EMT markers was monitored. The migratory ability was analysed following Snail overexpression and silencing. Snail expression was assessed in 500 tumour samples from premenopausal breast cancer patients, randomised to either 2 years of tamoxifen or no adjuvant treatment.Results:Exposure to 0.1% oxygen resulted in elevated levels of Snail protein, along with changes in vimentin and E-cadherin expression, and in addition increased migration of MDA-MB-468 cells. Overexpression of Snail increased the motility of MCF-7, T-47D and MDA-MB-231 cells, whereas silencing of the protein resulted in decreased migratory propensity of MCF-7, MDA-MB-468 and MDA-MB-231 cells. Moreover, nuclear Snail expression was associated with tumours of higher grade and proliferation rate, but not with disease recurrence. Interestingly, Snail negativity was associated with impaired tamoxifen response (P=0.048).Conclusions:Our results demonstrate that hypoxia induces Snail expression but generally not a migratory phenotype, suggesting that hypoxic cells are only partially pushed towards EMT. Furthermore, our study supports the link between Snail and clinically relevant features and treatment response.British Journal of Cancer advance online publication, 20 October 2009; doi:10.1038/sj.bjc.6605369 www.bjcancer.com. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1500154
- author
- Lundgren, Katja LU ; Nordenskjöld, B and Landberg, Göran LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- British Journal of Cancer
- volume
- 101
- pages
- 1769 - 1781
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000271666400016
- pmid:19844232
- scopus:70449527638
- pmid:19844232
- ISSN
- 1532-1827
- DOI
- 10.1038/sj.bjc.6605369
- language
- English
- LU publication?
- yes
- id
- 82c90a34-8484-44df-8c13-b395db8dfafb (old id 1500154)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19844232?dopt=Abstract
- date added to LUP
- 2016-04-04 08:55:05
- date last changed
- 2022-05-16 22:17:53
@article{82c90a34-8484-44df-8c13-b395db8dfafb,
abstract = {{Background:Hypoxia is an element of the tumour microenvironment that impacts upon numerous cellular factors linked to clinical aggressiveness in cancer. One such factor, Snail, a master regulator of the epithelial-mesenchymal transition (EMT), has been implicated in key tumour biological processes such as invasion and metastasis. In this study we set out to investigate regulation of EMT in hypoxia, and the importance of Snail in cell migration and clinical outcome in breast cancer.Methods:Four breast cancer cell lines were exposed to 0.1% oxygen and expression of EMT markers was monitored. The migratory ability was analysed following Snail overexpression and silencing. Snail expression was assessed in 500 tumour samples from premenopausal breast cancer patients, randomised to either 2 years of tamoxifen or no adjuvant treatment.Results:Exposure to 0.1% oxygen resulted in elevated levels of Snail protein, along with changes in vimentin and E-cadherin expression, and in addition increased migration of MDA-MB-468 cells. Overexpression of Snail increased the motility of MCF-7, T-47D and MDA-MB-231 cells, whereas silencing of the protein resulted in decreased migratory propensity of MCF-7, MDA-MB-468 and MDA-MB-231 cells. Moreover, nuclear Snail expression was associated with tumours of higher grade and proliferation rate, but not with disease recurrence. Interestingly, Snail negativity was associated with impaired tamoxifen response (P=0.048).Conclusions:Our results demonstrate that hypoxia induces Snail expression but generally not a migratory phenotype, suggesting that hypoxic cells are only partially pushed towards EMT. Furthermore, our study supports the link between Snail and clinically relevant features and treatment response.British Journal of Cancer advance online publication, 20 October 2009; doi:10.1038/sj.bjc.6605369 www.bjcancer.com.}},
author = {{Lundgren, Katja and Nordenskjöld, B and Landberg, Göran}},
issn = {{1532-1827}},
language = {{eng}},
pages = {{1769--1781}},
publisher = {{Nature Publishing Group}},
series = {{British Journal of Cancer}},
title = {{Hypoxia, Snail and incomplete epithelial-mesenchymal transition in breast cancer.}},
url = {{http://dx.doi.org/10.1038/sj.bjc.6605369}},
doi = {{10.1038/sj.bjc.6605369}},
volume = {{101}},
year = {{2009}},
}