Cargando…
Breast cancer metastasis suppressor 1 (BRMS1) attenuates TGF-β1-induced breast cancer cell aggressiveness through downregulating HIF-1α expression
BACKGROUND: Cancer metastasis is a multi-step event including epithelial-to-mesenchymal transition (EMT). Breast cancer metastasis suppressor 1 (BRMS1) is a novel metastasis suppressor protein without anti-proliferating activity. However, a detailed underlying mechanism by which BRMS1 attenuates can...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628375/ https://www.ncbi.nlm.nih.gov/pubmed/26520789 http://dx.doi.org/10.1186/s12885-015-1864-y |
_version_ | 1782398442157375488 |
---|---|
author | Cho, Kyung Hwa Yu, Seong-Lan Cho, Do Yeun Park, Chang Gyo Lee, Hoi Young |
author_facet | Cho, Kyung Hwa Yu, Seong-Lan Cho, Do Yeun Park, Chang Gyo Lee, Hoi Young |
author_sort | Cho, Kyung Hwa |
collection | PubMed |
description | BACKGROUND: Cancer metastasis is a multi-step event including epithelial-to-mesenchymal transition (EMT). Breast cancer metastasis suppressor 1 (BRMS1) is a novel metastasis suppressor protein without anti-proliferating activity. However, a detailed underlying mechanism by which BRMS1 attenuates cancer cell EMT and invasion remained to be answered. In the present study, we report an additional mechanism by which BRMS1 attenuates Transforming growth factor-beta1 (TGF-β1)-induced breast cancer cell EMT and invasion. METHODS: Experimental analysis involving chromosome immunoprecipitation (ChIP) and luciferase reporter assays were used to validate hypoxia inducible factor-1alpha (HIF-1α) as a transcriptional regulator of TWIST1 and Snail. Quantitative RT-PCR was used to analyze transcript expression. Immunoblotting and immunofluorescence were used to analyze protein expression. Matrigel-coated in vitro invasion insert was used to analyze cancer cell invasion. RESULTS: BRMS1 strongly inhibited TGF-β1-induced breast cancer cell EMT and invasion. Unexpectedly, we observed that BRMS1 downregulates not only TWIST1 but also Snail expression, thereby inhibiting breast cancer cell invasion. In addition, we provide evidence that HIF-1α is required for Snail and TWIST1 expression. Further, BRMS1 reduced TGF-β1-induced HIF-1α transcript expression through inactivation of nuclear factor kappaB (NF-κB). CONCLUSION: Collectively, the present study demonstrates a mechanical cascade of BRMS1 suppressing cancer cell invasion through downregulating HIF-1α transcript and consequently reducing Snail and TWIST1 expression. |
format | Online Article Text |
id | pubmed-4628375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46283752015-11-01 Breast cancer metastasis suppressor 1 (BRMS1) attenuates TGF-β1-induced breast cancer cell aggressiveness through downregulating HIF-1α expression Cho, Kyung Hwa Yu, Seong-Lan Cho, Do Yeun Park, Chang Gyo Lee, Hoi Young BMC Cancer Research Article BACKGROUND: Cancer metastasis is a multi-step event including epithelial-to-mesenchymal transition (EMT). Breast cancer metastasis suppressor 1 (BRMS1) is a novel metastasis suppressor protein without anti-proliferating activity. However, a detailed underlying mechanism by which BRMS1 attenuates cancer cell EMT and invasion remained to be answered. In the present study, we report an additional mechanism by which BRMS1 attenuates Transforming growth factor-beta1 (TGF-β1)-induced breast cancer cell EMT and invasion. METHODS: Experimental analysis involving chromosome immunoprecipitation (ChIP) and luciferase reporter assays were used to validate hypoxia inducible factor-1alpha (HIF-1α) as a transcriptional regulator of TWIST1 and Snail. Quantitative RT-PCR was used to analyze transcript expression. Immunoblotting and immunofluorescence were used to analyze protein expression. Matrigel-coated in vitro invasion insert was used to analyze cancer cell invasion. RESULTS: BRMS1 strongly inhibited TGF-β1-induced breast cancer cell EMT and invasion. Unexpectedly, we observed that BRMS1 downregulates not only TWIST1 but also Snail expression, thereby inhibiting breast cancer cell invasion. In addition, we provide evidence that HIF-1α is required for Snail and TWIST1 expression. Further, BRMS1 reduced TGF-β1-induced HIF-1α transcript expression through inactivation of nuclear factor kappaB (NF-κB). CONCLUSION: Collectively, the present study demonstrates a mechanical cascade of BRMS1 suppressing cancer cell invasion through downregulating HIF-1α transcript and consequently reducing Snail and TWIST1 expression. BioMed Central 2015-10-31 /pmc/articles/PMC4628375/ /pubmed/26520789 http://dx.doi.org/10.1186/s12885-015-1864-y Text en © Cho et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 Article Cho, Kyung Hwa Yu, Seong-Lan Cho, Do Yeun Park, Chang Gyo Lee, Hoi Young Breast cancer metastasis suppressor 1 (BRMS1) attenuates TGF-β1-induced breast cancer cell aggressiveness through downregulating HIF-1α expression |
title | Breast cancer metastasis suppressor 1 (BRMS1) attenuates TGF-β1-induced breast cancer cell aggressiveness through downregulating HIF-1α expression |
title_full | Breast cancer metastasis suppressor 1 (BRMS1) attenuates TGF-β1-induced breast cancer cell aggressiveness through downregulating HIF-1α expression |
title_fullStr | Breast cancer metastasis suppressor 1 (BRMS1) attenuates TGF-β1-induced breast cancer cell aggressiveness through downregulating HIF-1α expression |
title_full_unstemmed | Breast cancer metastasis suppressor 1 (BRMS1) attenuates TGF-β1-induced breast cancer cell aggressiveness through downregulating HIF-1α expression |
title_short | Breast cancer metastasis suppressor 1 (BRMS1) attenuates TGF-β1-induced breast cancer cell aggressiveness through downregulating HIF-1α expression |
title_sort | breast cancer metastasis suppressor 1 (brms1) attenuates tgf-β1-induced breast cancer cell aggressiveness through downregulating hif-1α expression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4628375/ https://www.ncbi.nlm.nih.gov/pubmed/26520789 http://dx.doi.org/10.1186/s12885-015-1864-y |
work_keys_str_mv | AT chokyunghwa breastcancermetastasissuppressor1brms1attenuatestgfb1inducedbreastcancercellaggressivenessthroughdownregulatinghif1aexpression AT yuseonglan breastcancermetastasissuppressor1brms1attenuatestgfb1inducedbreastcancercellaggressivenessthroughdownregulatinghif1aexpression AT chodoyeun breastcancermetastasissuppressor1brms1attenuatestgfb1inducedbreastcancercellaggressivenessthroughdownregulatinghif1aexpression AT parkchanggyo breastcancermetastasissuppressor1brms1attenuatestgfb1inducedbreastcancercellaggressivenessthroughdownregulatinghif1aexpression AT leehoiyoung breastcancermetastasissuppressor1brms1attenuatestgfb1inducedbreastcancercellaggressivenessthroughdownregulatinghif1aexpression |