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Interleukin-like EMT inducer regulates partial phenotype switching in MITF-low melanoma cell lines
ILEI (FAM3C) is a secreted factor that contributes to the epithelial-to-mesenchymal transition (EMT), a cell biological process that confers metastatic properties to a tumor cell. Initially, we found that ILEI mRNA is highly expressed in melanoma metastases but not in primary tumors, suggesting that...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435346/ https://www.ncbi.nlm.nih.gov/pubmed/28545079 http://dx.doi.org/10.1371/journal.pone.0177830 |
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author | Noguchi, Ken Dalton, Annamarie C. Howley, Breege V. McCall, Buckley J. Yoshida, Akihiro Diehl, J. Alan Howe, Philip H. |
author_facet | Noguchi, Ken Dalton, Annamarie C. Howley, Breege V. McCall, Buckley J. Yoshida, Akihiro Diehl, J. Alan Howe, Philip H. |
author_sort | Noguchi, Ken |
collection | PubMed |
description | ILEI (FAM3C) is a secreted factor that contributes to the epithelial-to-mesenchymal transition (EMT), a cell biological process that confers metastatic properties to a tumor cell. Initially, we found that ILEI mRNA is highly expressed in melanoma metastases but not in primary tumors, suggesting that ILEI contributes to the malignant properties of melanoma. While melanoma is not an epithelial cell-derived tumor and does not undergo a traditional EMT, melanoma undergoes a similar process known as phenotype switching in which high (micropthalmia-related transcription factor) MITF expressing (MITF-high) proliferative cells switch to a low expressing (MITF-low) invasive state. We observed that MITF-high proliferative cells express low levels of ILEI (ILEI-low) and MITF-low invasive cells express high levels of ILEI (ILEI-high). We found that inducing phenotype switching towards the MITF-low invasive state increases ILEI mRNA expression, whereas phenotype switching towards the MITF-high proliferative state decreases ILEI mRNA expression. Next, we used in vitro assays to show that knockdown of ILEI attenuates invasive potential but not MITF expression or chemoresistance. Finally, we used gene expression analysis to show that ILEI regulates several genes involved in the MITF-low invasive phenotype including JARID1B, HIF-2α, and BDNF. Gene set enrichment analysis suggested that ILEI-regulated genes are enriched for JUN signaling, a known regulator of the MITF-low invasive phenotype. In conclusion, we demonstrate that phenotype switching regulates ILEI expression, and that ILEI regulates partial phenotype switching in MITF-low melanoma cell lines. |
format | Online Article Text |
id | pubmed-5435346 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-54353462017-05-26 Interleukin-like EMT inducer regulates partial phenotype switching in MITF-low melanoma cell lines Noguchi, Ken Dalton, Annamarie C. Howley, Breege V. McCall, Buckley J. Yoshida, Akihiro Diehl, J. Alan Howe, Philip H. PLoS One Research Article ILEI (FAM3C) is a secreted factor that contributes to the epithelial-to-mesenchymal transition (EMT), a cell biological process that confers metastatic properties to a tumor cell. Initially, we found that ILEI mRNA is highly expressed in melanoma metastases but not in primary tumors, suggesting that ILEI contributes to the malignant properties of melanoma. While melanoma is not an epithelial cell-derived tumor and does not undergo a traditional EMT, melanoma undergoes a similar process known as phenotype switching in which high (micropthalmia-related transcription factor) MITF expressing (MITF-high) proliferative cells switch to a low expressing (MITF-low) invasive state. We observed that MITF-high proliferative cells express low levels of ILEI (ILEI-low) and MITF-low invasive cells express high levels of ILEI (ILEI-high). We found that inducing phenotype switching towards the MITF-low invasive state increases ILEI mRNA expression, whereas phenotype switching towards the MITF-high proliferative state decreases ILEI mRNA expression. Next, we used in vitro assays to show that knockdown of ILEI attenuates invasive potential but not MITF expression or chemoresistance. Finally, we used gene expression analysis to show that ILEI regulates several genes involved in the MITF-low invasive phenotype including JARID1B, HIF-2α, and BDNF. Gene set enrichment analysis suggested that ILEI-regulated genes are enriched for JUN signaling, a known regulator of the MITF-low invasive phenotype. In conclusion, we demonstrate that phenotype switching regulates ILEI expression, and that ILEI regulates partial phenotype switching in MITF-low melanoma cell lines. Public Library of Science 2017-05-17 /pmc/articles/PMC5435346/ /pubmed/28545079 http://dx.doi.org/10.1371/journal.pone.0177830 Text en © 2017 Noguchi et al http://creativecommons.org/licenses/by/4.0/ 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 author and source are credited. |
spellingShingle | Research Article Noguchi, Ken Dalton, Annamarie C. Howley, Breege V. McCall, Buckley J. Yoshida, Akihiro Diehl, J. Alan Howe, Philip H. Interleukin-like EMT inducer regulates partial phenotype switching in MITF-low melanoma cell lines |
title | Interleukin-like EMT inducer regulates partial phenotype switching in MITF-low melanoma cell lines |
title_full | Interleukin-like EMT inducer regulates partial phenotype switching in MITF-low melanoma cell lines |
title_fullStr | Interleukin-like EMT inducer regulates partial phenotype switching in MITF-low melanoma cell lines |
title_full_unstemmed | Interleukin-like EMT inducer regulates partial phenotype switching in MITF-low melanoma cell lines |
title_short | Interleukin-like EMT inducer regulates partial phenotype switching in MITF-low melanoma cell lines |
title_sort | interleukin-like emt inducer regulates partial phenotype switching in mitf-low melanoma cell lines |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435346/ https://www.ncbi.nlm.nih.gov/pubmed/28545079 http://dx.doi.org/10.1371/journal.pone.0177830 |
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