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Glycoprotein non–metastatic melanoma protein B functions with growth factor signaling to induce tumorigenesis through its serine phosphorylation
Breast cancer is the most common cancer among women. Glycoprotein non–metastatic melanoma protein B (GPNMB), a type I transmembrane protein that is highly expressed in many cancers, including breast cancer, has been shown to be a prognostic factor. We previously reported that GPNMB overexpression co...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486197/ https://www.ncbi.nlm.nih.gov/pubmed/34327762 http://dx.doi.org/10.1111/cas.15090 |
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author | Wang, Chen Okita, Yukari Zheng, Ling Shinkai, Yasuhiro Manevich, Lev Chin, Jas M. Kimura, Tomokazu Suzuki, Hiroyuki Kumagai, Yoshito Kato, Mitsuyasu |
author_facet | Wang, Chen Okita, Yukari Zheng, Ling Shinkai, Yasuhiro Manevich, Lev Chin, Jas M. Kimura, Tomokazu Suzuki, Hiroyuki Kumagai, Yoshito Kato, Mitsuyasu |
author_sort | Wang, Chen |
collection | PubMed |
description | Breast cancer is the most common cancer among women. Glycoprotein non–metastatic melanoma protein B (GPNMB), a type I transmembrane protein that is highly expressed in many cancers, including breast cancer, has been shown to be a prognostic factor. We previously reported that GPNMB overexpression confers tumorigenic potential, as evidenced by invasive tumor growth in vivo, sphere formation, and cellular migration and invasion to non–tumorigenic mammary epithelial cells. In this study, we focused on the serine (S) residue in the intracellular domain of GPNMB (S530 in human isoform b and S546 in mouse), which is predicted to be a phosphorylation site. To investigate the roles of this serine residue, we made an antibody specific for S530‐phosphorylated human GPNMB and a point mutant in which S530 is replaced by an alanine (A) residue, GPNMB(SA). Established GPNMB(SA) overexpressing cells showed a significant reduction in sphere formation in vitro and tumor growth in vivo as a result of decreased stemness‐related gene expression compared to that in GPNMB(WT)‐expressing cells. In addition, GPNMB(SA) impaired GPNMB‐mediated cellular migration. Furthermore, we found that tyrosine kinase receptor signaling triggered by epidermal growth factor or fibroblast growth factor 2 induces the serine phosphorylation of GPNMB through activation of downstream oncoproteins RAS and RAF. |
format | Online Article Text |
id | pubmed-8486197 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84861972021-10-07 Glycoprotein non–metastatic melanoma protein B functions with growth factor signaling to induce tumorigenesis through its serine phosphorylation Wang, Chen Okita, Yukari Zheng, Ling Shinkai, Yasuhiro Manevich, Lev Chin, Jas M. Kimura, Tomokazu Suzuki, Hiroyuki Kumagai, Yoshito Kato, Mitsuyasu Cancer Sci Original Articles Breast cancer is the most common cancer among women. Glycoprotein non–metastatic melanoma protein B (GPNMB), a type I transmembrane protein that is highly expressed in many cancers, including breast cancer, has been shown to be a prognostic factor. We previously reported that GPNMB overexpression confers tumorigenic potential, as evidenced by invasive tumor growth in vivo, sphere formation, and cellular migration and invasion to non–tumorigenic mammary epithelial cells. In this study, we focused on the serine (S) residue in the intracellular domain of GPNMB (S530 in human isoform b and S546 in mouse), which is predicted to be a phosphorylation site. To investigate the roles of this serine residue, we made an antibody specific for S530‐phosphorylated human GPNMB and a point mutant in which S530 is replaced by an alanine (A) residue, GPNMB(SA). Established GPNMB(SA) overexpressing cells showed a significant reduction in sphere formation in vitro and tumor growth in vivo as a result of decreased stemness‐related gene expression compared to that in GPNMB(WT)‐expressing cells. In addition, GPNMB(SA) impaired GPNMB‐mediated cellular migration. Furthermore, we found that tyrosine kinase receptor signaling triggered by epidermal growth factor or fibroblast growth factor 2 induces the serine phosphorylation of GPNMB through activation of downstream oncoproteins RAS and RAF. John Wiley and Sons Inc. 2021-08-10 2021-10 /pmc/articles/PMC8486197/ /pubmed/34327762 http://dx.doi.org/10.1111/cas.15090 Text en © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Wang, Chen Okita, Yukari Zheng, Ling Shinkai, Yasuhiro Manevich, Lev Chin, Jas M. Kimura, Tomokazu Suzuki, Hiroyuki Kumagai, Yoshito Kato, Mitsuyasu Glycoprotein non–metastatic melanoma protein B functions with growth factor signaling to induce tumorigenesis through its serine phosphorylation |
title | Glycoprotein non–metastatic melanoma protein B functions with growth factor signaling to induce tumorigenesis through its serine phosphorylation |
title_full | Glycoprotein non–metastatic melanoma protein B functions with growth factor signaling to induce tumorigenesis through its serine phosphorylation |
title_fullStr | Glycoprotein non–metastatic melanoma protein B functions with growth factor signaling to induce tumorigenesis through its serine phosphorylation |
title_full_unstemmed | Glycoprotein non–metastatic melanoma protein B functions with growth factor signaling to induce tumorigenesis through its serine phosphorylation |
title_short | Glycoprotein non–metastatic melanoma protein B functions with growth factor signaling to induce tumorigenesis through its serine phosphorylation |
title_sort | glycoprotein non–metastatic melanoma protein b functions with growth factor signaling to induce tumorigenesis through its serine phosphorylation |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486197/ https://www.ncbi.nlm.nih.gov/pubmed/34327762 http://dx.doi.org/10.1111/cas.15090 |
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