Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells
Breast cancer metastasizes to bone, visceral organs, and/or brain depending on the subtype, which may involve activation of a host organ-specific signaling network in metastatic cells. To test this possibility, we determined gene expression patterns in MDA-MB-231 cells and its mammary fat pad tumor...
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Impact Journals LLC
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494966/ |
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pubmed-4494966 |
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pubmed-44949662015-07-13 Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells Burnett, Riesa M. Craven, Kelly E. Krishnamurthy, Purna Goswami, Chirayu P. Badve, Sunil Crooks, Peter Mathews, William P. Bhat-Nakshatri, Poornima Nakshatri, Harikrishna Research Paper Breast cancer metastasizes to bone, visceral organs, and/or brain depending on the subtype, which may involve activation of a host organ-specific signaling network in metastatic cells. To test this possibility, we determined gene expression patterns in MDA-MB-231 cells and its mammary fat pad tumor (TMD-231), lung-metastasis (LMD-231), bone-metastasis (BMD-231), adrenal-metastasis (ADMD-231) and brain-metastasis (231-BR) variants. When gene expression between metastases was compared, 231-BR cells showed the highest gene expression difference followed by ADMD-231, LMD-231, and BMD-231 cells. Neuronal transmembrane proteins SLITRK2, TMEM47, and LYPD1 were specifically overexpressed in 231-BR cells. Pathway-analyses revealed activation of signaling networks that would enable cancer cells to adapt to organs of metastasis such as drug detoxification/oxidative stress response/semaphorin neuronal pathway in 231-BR, Notch/orphan nuclear receptor signals involved in steroidogenesis in ADMD-231, acute phase response in LMD-231, and cytokine/hematopoietic stem cell signaling in BMD-231 cells. Only NF-κB signaling pathway activation was common to all except BMD-231 cells. We confirmed NF-κB activation in 231-BR and in a brain metastatic variant of 4T1 cells (4T1-BR). Dimethylaminoparthenolide inhibited NF-κB activity, LYPD1 expression, and proliferation of 231-BR and 4T1-BR cells. Thus, transcriptome change enabling adaptation to host organs is likely one of the mechanisms associated with organ-specific metastasis and could potentially be targeted therapeutically. Impact Journals LLC 2015-03-30 /pmc/articles/PMC4494966/ /pubmed/25926557 Text en Copyright: © 2015 Burnett et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Burnett, Riesa M. Craven, Kelly E. Krishnamurthy, Purna Goswami, Chirayu P. Badve, Sunil Crooks, Peter Mathews, William P. Bhat-Nakshatri, Poornima Nakshatri, Harikrishna |
| spellingShingle |
Burnett, Riesa M. Craven, Kelly E. Krishnamurthy, Purna Goswami, Chirayu P. Badve, Sunil Crooks, Peter Mathews, William P. Bhat-Nakshatri, Poornima Nakshatri, Harikrishna Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells |
| author_facet |
Burnett, Riesa M. Craven, Kelly E. Krishnamurthy, Purna Goswami, Chirayu P. Badve, Sunil Crooks, Peter Mathews, William P. Bhat-Nakshatri, Poornima Nakshatri, Harikrishna |
| author_sort |
Burnett, Riesa M. |
| title |
Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells |
| title_short |
Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells |
| title_full |
Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells |
| title_fullStr |
Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells |
| title_full_unstemmed |
Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells |
| title_sort |
organ-specific adaptive signaling pathway activation in metastatic breast cancer cells |
| description |
Breast cancer metastasizes to bone, visceral organs, and/or brain depending on the subtype, which may involve activation of a host organ-specific signaling network in metastatic cells. To test this possibility, we determined gene expression patterns in MDA-MB-231 cells and its mammary fat pad tumor (TMD-231), lung-metastasis (LMD-231), bone-metastasis (BMD-231), adrenal-metastasis (ADMD-231) and brain-metastasis (231-BR) variants. When gene expression between metastases was compared, 231-BR cells showed the highest gene expression difference followed by ADMD-231, LMD-231, and BMD-231 cells. Neuronal transmembrane proteins SLITRK2, TMEM47, and LYPD1 were specifically overexpressed in 231-BR cells. Pathway-analyses revealed activation of signaling networks that would enable cancer cells to adapt to organs of metastasis such as drug detoxification/oxidative stress response/semaphorin neuronal pathway in 231-BR, Notch/orphan nuclear receptor signals involved in steroidogenesis in ADMD-231, acute phase response in LMD-231, and cytokine/hematopoietic stem cell signaling in BMD-231 cells. Only NF-κB signaling pathway activation was common to all except BMD-231 cells. We confirmed NF-κB activation in 231-BR and in a brain metastatic variant of 4T1 cells (4T1-BR). Dimethylaminoparthenolide inhibited NF-κB activity, LYPD1 expression, and proliferation of 231-BR and 4T1-BR cells. Thus, transcriptome change enabling adaptation to host organs is likely one of the mechanisms associated with organ-specific metastasis and could potentially be targeted therapeutically. |
| publisher |
Impact Journals LLC |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494966/ |
| _version_ |
1613245322565255168 |