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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...

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Autores principales: Wang, Chen, Okita, Yukari, Zheng, Ling, Shinkai, Yasuhiro, Manevich, Lev, Chin, Jas M., Kimura, Tomokazu, Suzuki, Hiroyuki, Kumagai, Yoshito, Kato, Mitsuyasu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
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.
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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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