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Overexpression of the nucleoporin Nup88 stimulates migration and invasion of HeLa cells

Elevated expression of the nucleoporin Nup88, a constituent of the nuclear pore complex, is seen in various types of malignant tumors, but whether this overexpression contributes to the malignant phenotype has yet to be determined. Here, we investigated the effect of the overexpression of Nup88 on t...

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Autores principales: Makise, Masaki, Uchimura, Ryota, Higashi, Kumiko, Mashiki, Yasumi, Shiraishi, Rikako, Shutoku, Yuumi, Kuniyasu, Akihiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604841/
https://www.ncbi.nlm.nih.gov/pubmed/34331103
http://dx.doi.org/10.1007/s00418-021-02020-w
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author Makise, Masaki
Uchimura, Ryota
Higashi, Kumiko
Mashiki, Yasumi
Shiraishi, Rikako
Shutoku, Yuumi
Kuniyasu, Akihiko
author_facet Makise, Masaki
Uchimura, Ryota
Higashi, Kumiko
Mashiki, Yasumi
Shiraishi, Rikako
Shutoku, Yuumi
Kuniyasu, Akihiko
author_sort Makise, Masaki
collection PubMed
description Elevated expression of the nucleoporin Nup88, a constituent of the nuclear pore complex, is seen in various types of malignant tumors, but whether this overexpression contributes to the malignant phenotype has yet to be determined. Here, we investigated the effect of the overexpression of Nup88 on the migration and invasion of cervical cancer HeLa cells. The overexpression of Nup88 promoted a slight but significant increase in both migration and invasion, whereas knockdown of Nup88 by RNA interference suppressed these phenotypes. The observed phenotypes in Nup88-overexpressing HeLa cells were not due to the progression of the epithelial-to-mesenchymal transition or activation of NF-κB, which are known to be important for cell migration and invasion. Instead, we identified an upregulation of matrix metalloproteinase-12 (MMP-12) at both the gene and protein levels in Nup88-overexpressing HeLa cells. Upregulation of MMP-12 protein by the overexpression of Nup88 was also observed in one other cervical cancer cell line and two prostate cancer cell lines but not 293 cells. Treatment with a selective inhibitor against MMP-12 enzymatic activity significantly suppressed the invasive ability of HeLa cells induced by Nup88 overexpression. Taken together, our results suggest that overexpression of Nup88 can stimulate malignant phenotypes including invasive ability, which is promoted by MMP-12 expression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00418-021-02020-w.
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spelling pubmed-86048412021-12-03 Overexpression of the nucleoporin Nup88 stimulates migration and invasion of HeLa cells Makise, Masaki Uchimura, Ryota Higashi, Kumiko Mashiki, Yasumi Shiraishi, Rikako Shutoku, Yuumi Kuniyasu, Akihiko Histochem Cell Biol Original Paper Elevated expression of the nucleoporin Nup88, a constituent of the nuclear pore complex, is seen in various types of malignant tumors, but whether this overexpression contributes to the malignant phenotype has yet to be determined. Here, we investigated the effect of the overexpression of Nup88 on the migration and invasion of cervical cancer HeLa cells. The overexpression of Nup88 promoted a slight but significant increase in both migration and invasion, whereas knockdown of Nup88 by RNA interference suppressed these phenotypes. The observed phenotypes in Nup88-overexpressing HeLa cells were not due to the progression of the epithelial-to-mesenchymal transition or activation of NF-κB, which are known to be important for cell migration and invasion. Instead, we identified an upregulation of matrix metalloproteinase-12 (MMP-12) at both the gene and protein levels in Nup88-overexpressing HeLa cells. Upregulation of MMP-12 protein by the overexpression of Nup88 was also observed in one other cervical cancer cell line and two prostate cancer cell lines but not 293 cells. Treatment with a selective inhibitor against MMP-12 enzymatic activity significantly suppressed the invasive ability of HeLa cells induced by Nup88 overexpression. Taken together, our results suggest that overexpression of Nup88 can stimulate malignant phenotypes including invasive ability, which is promoted by MMP-12 expression. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00418-021-02020-w. Springer Berlin Heidelberg 2021-07-31 2021 /pmc/articles/PMC8604841/ /pubmed/34331103 http://dx.doi.org/10.1007/s00418-021-02020-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Paper
Makise, Masaki
Uchimura, Ryota
Higashi, Kumiko
Mashiki, Yasumi
Shiraishi, Rikako
Shutoku, Yuumi
Kuniyasu, Akihiko
Overexpression of the nucleoporin Nup88 stimulates migration and invasion of HeLa cells
title Overexpression of the nucleoporin Nup88 stimulates migration and invasion of HeLa cells
title_full Overexpression of the nucleoporin Nup88 stimulates migration and invasion of HeLa cells
title_fullStr Overexpression of the nucleoporin Nup88 stimulates migration and invasion of HeLa cells
title_full_unstemmed Overexpression of the nucleoporin Nup88 stimulates migration and invasion of HeLa cells
title_short Overexpression of the nucleoporin Nup88 stimulates migration and invasion of HeLa cells
title_sort overexpression of the nucleoporin nup88 stimulates migration and invasion of hela cells
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604841/
https://www.ncbi.nlm.nih.gov/pubmed/34331103
http://dx.doi.org/10.1007/s00418-021-02020-w
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