Cargando…
Sphingosine-1-Phosphate Induces the Migration of Thyroid Follicular Carcinoma Cells through the MicroRNA-17/PTK6/ERK1/2 Pathway
Sphingosine-1-phosphate (S1P) is a bioactive lipid known to play a role in tumorigenesis and cancer progression. However, the molecular mechanisms of S1P regulated migration of papillary thyroid cancer cells are still unknown. In this study, we showed that S1P induced PTK6 mRNA and protein expressio...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351951/ https://www.ncbi.nlm.nih.gov/pubmed/25748447 http://dx.doi.org/10.1371/journal.pone.0119148 |
_version_ | 1782360383948849152 |
---|---|
author | Zhao, Shitao Li, Jincheng |
author_facet | Zhao, Shitao Li, Jincheng |
author_sort | Zhao, Shitao |
collection | PubMed |
description | Sphingosine-1-phosphate (S1P) is a bioactive lipid known to play a role in tumorigenesis and cancer progression. However, the molecular mechanisms of S1P regulated migration of papillary thyroid cancer cells are still unknown. In this study, we showed that S1P induced PTK6 mRNA and protein expression in two thyroid follicular cancer cell lines (ML-1 and FTC-133). Further studies demonstrated that induced PTK6 and its downstream signal component (ERK1/2) are involved in S1P-induced migration. Upon investigating the mechanisms behind this event, we found that miR-17 inhibited the expression of PTK6 through direct binding to its 3’-UTR. Through overexpression and knockdown studies, we found that miR-17 can significantly inhibit S1P-induced migration in thyroid follicular cancer cells. Interestingly, overexpression or knockdown of PTK6 or ERK1/2 effectively removed the inhibition of S1P-induced migration by miR-17. Furthermore, we showed that S1P decreased miR-17 expression levels. Meanwhile, in papillary thyroid cancers, miR-17 is downregulated and negatively associated with clinical staging, whereas PTK6 is upregulated and positively associated with clinical stages. Collectively, our work defines a novel signaling pathway implicated in the control of thyroid cancer migration. |
format | Online Article Text |
id | pubmed-4351951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43519512015-03-17 Sphingosine-1-Phosphate Induces the Migration of Thyroid Follicular Carcinoma Cells through the MicroRNA-17/PTK6/ERK1/2 Pathway Zhao, Shitao Li, Jincheng PLoS One Research Article Sphingosine-1-phosphate (S1P) is a bioactive lipid known to play a role in tumorigenesis and cancer progression. However, the molecular mechanisms of S1P regulated migration of papillary thyroid cancer cells are still unknown. In this study, we showed that S1P induced PTK6 mRNA and protein expression in two thyroid follicular cancer cell lines (ML-1 and FTC-133). Further studies demonstrated that induced PTK6 and its downstream signal component (ERK1/2) are involved in S1P-induced migration. Upon investigating the mechanisms behind this event, we found that miR-17 inhibited the expression of PTK6 through direct binding to its 3’-UTR. Through overexpression and knockdown studies, we found that miR-17 can significantly inhibit S1P-induced migration in thyroid follicular cancer cells. Interestingly, overexpression or knockdown of PTK6 or ERK1/2 effectively removed the inhibition of S1P-induced migration by miR-17. Furthermore, we showed that S1P decreased miR-17 expression levels. Meanwhile, in papillary thyroid cancers, miR-17 is downregulated and negatively associated with clinical staging, whereas PTK6 is upregulated and positively associated with clinical stages. Collectively, our work defines a novel signaling pathway implicated in the control of thyroid cancer migration. Public Library of Science 2015-03-06 /pmc/articles/PMC4351951/ /pubmed/25748447 http://dx.doi.org/10.1371/journal.pone.0119148 Text en © 2015 Zhao, Li http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Zhao, Shitao Li, Jincheng Sphingosine-1-Phosphate Induces the Migration of Thyroid Follicular Carcinoma Cells through the MicroRNA-17/PTK6/ERK1/2 Pathway |
title | Sphingosine-1-Phosphate Induces the Migration of Thyroid Follicular Carcinoma Cells through the MicroRNA-17/PTK6/ERK1/2 Pathway |
title_full | Sphingosine-1-Phosphate Induces the Migration of Thyroid Follicular Carcinoma Cells through the MicroRNA-17/PTK6/ERK1/2 Pathway |
title_fullStr | Sphingosine-1-Phosphate Induces the Migration of Thyroid Follicular Carcinoma Cells through the MicroRNA-17/PTK6/ERK1/2 Pathway |
title_full_unstemmed | Sphingosine-1-Phosphate Induces the Migration of Thyroid Follicular Carcinoma Cells through the MicroRNA-17/PTK6/ERK1/2 Pathway |
title_short | Sphingosine-1-Phosphate Induces the Migration of Thyroid Follicular Carcinoma Cells through the MicroRNA-17/PTK6/ERK1/2 Pathway |
title_sort | sphingosine-1-phosphate induces the migration of thyroid follicular carcinoma cells through the microrna-17/ptk6/erk1/2 pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351951/ https://www.ncbi.nlm.nih.gov/pubmed/25748447 http://dx.doi.org/10.1371/journal.pone.0119148 |
work_keys_str_mv | AT zhaoshitao sphingosine1phosphateinducesthemigrationofthyroidfollicularcarcinomacellsthroughthemicrorna17ptk6erk12pathway AT lijincheng sphingosine1phosphateinducesthemigrationofthyroidfollicularcarcinomacellsthroughthemicrorna17ptk6erk12pathway |