Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Noguchi, Ken, Dalton, Annamarie C., Howley, Breege V., McCall, Buckley J., Yoshida, Akihiro, Diehl, J. Alan, Howe, Philip H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
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
_version_ 1783237219930079232
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
work_keys_str_mv AT noguchiken interleukinlikeemtinducerregulatespartialphenotypeswitchinginmitflowmelanomacelllines
AT daltonannamariec interleukinlikeemtinducerregulatespartialphenotypeswitchinginmitflowmelanomacelllines
AT howleybreegev interleukinlikeemtinducerregulatespartialphenotypeswitchinginmitflowmelanomacelllines
AT mccallbuckleyj interleukinlikeemtinducerregulatespartialphenotypeswitchinginmitflowmelanomacelllines
AT yoshidaakihiro interleukinlikeemtinducerregulatespartialphenotypeswitchinginmitflowmelanomacelllines
AT diehljalan interleukinlikeemtinducerregulatespartialphenotypeswitchinginmitflowmelanomacelllines
AT howephiliph interleukinlikeemtinducerregulatespartialphenotypeswitchinginmitflowmelanomacelllines