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β-1,3-Galactosyl-O-Glycosyl-Glycoprotein β-1,6-N-Acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility
We previously identified novel S100A8/A9 receptors, extracellular matrix metalloproteinase inducer (EMMPRIN), melanoma cell adhesion molecule (MCAM), activated leukocyte cell adhesion molecule (ALCAM), and neuroplastin (NPTN) β, that are critically involved in S100A8/A9-mediated cancer metastasis an...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Cognizant Communication Corporation
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844831/ https://www.ncbi.nlm.nih.gov/pubmed/28923134 http://dx.doi.org/10.3727/096504017X15031557924123 |
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author | Sumardika, I Wayan Youyi, Chen Kondo, Eisaku Inoue, Yusuke Ruma, I Made Winarsa Murata, Hitoshi Kinoshita, Rie Yamamoto, Ken-Ichi Tomida, Shuta Shien, Kazuhiko Sato, Hiroki Yamauchi, Akira Futami, Junichiro Putranto, Endy Widya Hibino, Toshihiko Toyooka, Shinichi Nishibori, Masahiro Sakaguchi, Masakiyo |
author_facet | Sumardika, I Wayan Youyi, Chen Kondo, Eisaku Inoue, Yusuke Ruma, I Made Winarsa Murata, Hitoshi Kinoshita, Rie Yamamoto, Ken-Ichi Tomida, Shuta Shien, Kazuhiko Sato, Hiroki Yamauchi, Akira Futami, Junichiro Putranto, Endy Widya Hibino, Toshihiko Toyooka, Shinichi Nishibori, Masahiro Sakaguchi, Masakiyo |
author_sort | Sumardika, I Wayan |
collection | PubMed |
description | We previously identified novel S100A8/A9 receptors, extracellular matrix metalloproteinase inducer (EMMPRIN), melanoma cell adhesion molecule (MCAM), activated leukocyte cell adhesion molecule (ALCAM), and neuroplastin (NPTN) β, that are critically involved in S100A8/A9-mediated cancer metastasis and inflammation when expressed at high levels. However, little is known about the presence of any cancer-specific mechanism(s) that modifies these receptors, further inducing upregulation at protein levels without any transcriptional regulation. Expression levels of glycosyltransferase-encoding genes were examined by a PCR-based profiling array followed by confirmation with quantitative real-time PCR. Cell migration and invasion were assessed using a Boyden chamber. Western blotting was used to examine the protein level, and the RNA level was examined by Northern blotting. Immunohistochemistry was used to examine the expression pattern of β-1,3-galactosyl-O-glycosyl-glycoprotein β-1,6-N-acetylglucosaminyltransferase 3 (GCNT3) and MCAM in melanoma tissue. We found that GCNT3 is overexpressed in highly metastatic melanomas. Silencing and functional inhibition of GCNT3 greatly suppressed migration and invasion of melanoma cells, resulting in the loss of S100A8/A9 responsiveness. Among the novel S100A8/A9 receptors, GCNT3 favorably glycosylates the MCAM receptor, extending its half-life and leading to further elevation of S100A8/A9-mediated cellular motility in melanoma cells. GCNT3 expression is positively correlated to MCAM expression in patients with high-grade melanomas. Collectively, our results showed that GCNT3 is an upstream regulator of MCAM protein and indicate the possibility of a potential molecular target in melanoma therapeutics through abrogation of the S100A8/A9–MCAM axis. |
format | Online Article Text |
id | pubmed-7844831 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cognizant Communication Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-78448312021-02-16 β-1,3-Galactosyl-O-Glycosyl-Glycoprotein β-1,6-N-Acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility Sumardika, I Wayan Youyi, Chen Kondo, Eisaku Inoue, Yusuke Ruma, I Made Winarsa Murata, Hitoshi Kinoshita, Rie Yamamoto, Ken-Ichi Tomida, Shuta Shien, Kazuhiko Sato, Hiroki Yamauchi, Akira Futami, Junichiro Putranto, Endy Widya Hibino, Toshihiko Toyooka, Shinichi Nishibori, Masahiro Sakaguchi, Masakiyo Oncol Res Article We previously identified novel S100A8/A9 receptors, extracellular matrix metalloproteinase inducer (EMMPRIN), melanoma cell adhesion molecule (MCAM), activated leukocyte cell adhesion molecule (ALCAM), and neuroplastin (NPTN) β, that are critically involved in S100A8/A9-mediated cancer metastasis and inflammation when expressed at high levels. However, little is known about the presence of any cancer-specific mechanism(s) that modifies these receptors, further inducing upregulation at protein levels without any transcriptional regulation. Expression levels of glycosyltransferase-encoding genes were examined by a PCR-based profiling array followed by confirmation with quantitative real-time PCR. Cell migration and invasion were assessed using a Boyden chamber. Western blotting was used to examine the protein level, and the RNA level was examined by Northern blotting. Immunohistochemistry was used to examine the expression pattern of β-1,3-galactosyl-O-glycosyl-glycoprotein β-1,6-N-acetylglucosaminyltransferase 3 (GCNT3) and MCAM in melanoma tissue. We found that GCNT3 is overexpressed in highly metastatic melanomas. Silencing and functional inhibition of GCNT3 greatly suppressed migration and invasion of melanoma cells, resulting in the loss of S100A8/A9 responsiveness. Among the novel S100A8/A9 receptors, GCNT3 favorably glycosylates the MCAM receptor, extending its half-life and leading to further elevation of S100A8/A9-mediated cellular motility in melanoma cells. GCNT3 expression is positively correlated to MCAM expression in patients with high-grade melanomas. Collectively, our results showed that GCNT3 is an upstream regulator of MCAM protein and indicate the possibility of a potential molecular target in melanoma therapeutics through abrogation of the S100A8/A9–MCAM axis. Cognizant Communication Corporation 2018-04-10 /pmc/articles/PMC7844831/ /pubmed/28923134 http://dx.doi.org/10.3727/096504017X15031557924123 Text en Copyright © 2018 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License. |
spellingShingle | Article Sumardika, I Wayan Youyi, Chen Kondo, Eisaku Inoue, Yusuke Ruma, I Made Winarsa Murata, Hitoshi Kinoshita, Rie Yamamoto, Ken-Ichi Tomida, Shuta Shien, Kazuhiko Sato, Hiroki Yamauchi, Akira Futami, Junichiro Putranto, Endy Widya Hibino, Toshihiko Toyooka, Shinichi Nishibori, Masahiro Sakaguchi, Masakiyo β-1,3-Galactosyl-O-Glycosyl-Glycoprotein β-1,6-N-Acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility |
title | β-1,3-Galactosyl-O-Glycosyl-Glycoprotein β-1,6-N-Acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility |
title_full | β-1,3-Galactosyl-O-Glycosyl-Glycoprotein β-1,6-N-Acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility |
title_fullStr | β-1,3-Galactosyl-O-Glycosyl-Glycoprotein β-1,6-N-Acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility |
title_full_unstemmed | β-1,3-Galactosyl-O-Glycosyl-Glycoprotein β-1,6-N-Acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility |
title_short | β-1,3-Galactosyl-O-Glycosyl-Glycoprotein β-1,6-N-Acetylglucosaminyltransferase 3 Increases MCAM Stability, Which Enhances S100A8/A9-Mediated Cancer Motility |
title_sort | β-1,3-galactosyl-o-glycosyl-glycoprotein β-1,6-n-acetylglucosaminyltransferase 3 increases mcam stability, which enhances s100a8/a9-mediated cancer motility |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844831/ https://www.ncbi.nlm.nih.gov/pubmed/28923134 http://dx.doi.org/10.3727/096504017X15031557924123 |
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