Cargando…

Ribitol enhances matriglycan of α-dystroglycan in breast cancer cells without affecting cell growth

The laminin-binding glycan (matriglycan) on α-dystroglycan (α-DG) enables diverse roles, from neuronal development to muscle integrity. Reduction or loss of matriglycan has also been implicated in cancer development and metastasis, and specifically associated with high-grade tumors and poor prognose...

Descripción completa

Detalles Bibliográficos
Autores principales: Lu, Pei J., Tucker, Jason D., Branch, Elizabeth K., Guo, Fei, Blaeser, Anthony R., Lu, Qi L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080755/
https://www.ncbi.nlm.nih.gov/pubmed/32188898
http://dx.doi.org/10.1038/s41598-020-61747-z
_version_ 1783508056539136000
author Lu, Pei J.
Tucker, Jason D.
Branch, Elizabeth K.
Guo, Fei
Blaeser, Anthony R.
Lu, Qi L.
author_facet Lu, Pei J.
Tucker, Jason D.
Branch, Elizabeth K.
Guo, Fei
Blaeser, Anthony R.
Lu, Qi L.
author_sort Lu, Pei J.
collection PubMed
description The laminin-binding glycan (matriglycan) on α-dystroglycan (α-DG) enables diverse roles, from neuronal development to muscle integrity. Reduction or loss of matriglycan has also been implicated in cancer development and metastasis, and specifically associated with high-grade tumors and poor prognoses in breast cancers. Hyperglycosylation of α-DG with LARGE overexpression is shown to inhibit cancer cell growth and tumorigenicity. We recently demonstrated that ribitol, considered to be a metabolic end-product, enhances matriglycan expression in dystrophic muscles in vivo. In the current study, we tested the hypothesis that ribitol could also enhance matriglycan expression in cancer cells. Our results showed for the first time that ribitol is able to significantly enhance the expression of matriglycan on α-DG in breast cancer cells. The ribitol effect is associated with an increase in levels of CDP-ribitol, the substrate for the ribitol-5-phosphate transferases FKRP and FKTN. Direct use of CDP-ribitol is also effective for matriglycan expression. Ribitol treatment does not alter the expression of FKRP, FKTN as well as LARGEs and ISPD which are critical for the synthesis of matriglycan. The results suggest that alteration in substrates could also be involved in regulation of matriglycan expression. Interestingly, expression of matriglycan is related to cell cycle progression with highest levels in S and G2 phases and ribitol treatment does not alter the pattern. Although matriglycan up-regulation does not affect cell cycle progression and proliferation of the cancer cells tested, the novel substrate-mediated treatment opens a new approach easily applicable to experimental systems in vivo for further exploitation of matriglycan expression in cancer progression and for therapeutic potential.
format Online
Article
Text
id pubmed-7080755
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-70807552020-03-23 Ribitol enhances matriglycan of α-dystroglycan in breast cancer cells without affecting cell growth Lu, Pei J. Tucker, Jason D. Branch, Elizabeth K. Guo, Fei Blaeser, Anthony R. Lu, Qi L. Sci Rep Article The laminin-binding glycan (matriglycan) on α-dystroglycan (α-DG) enables diverse roles, from neuronal development to muscle integrity. Reduction or loss of matriglycan has also been implicated in cancer development and metastasis, and specifically associated with high-grade tumors and poor prognoses in breast cancers. Hyperglycosylation of α-DG with LARGE overexpression is shown to inhibit cancer cell growth and tumorigenicity. We recently demonstrated that ribitol, considered to be a metabolic end-product, enhances matriglycan expression in dystrophic muscles in vivo. In the current study, we tested the hypothesis that ribitol could also enhance matriglycan expression in cancer cells. Our results showed for the first time that ribitol is able to significantly enhance the expression of matriglycan on α-DG in breast cancer cells. The ribitol effect is associated with an increase in levels of CDP-ribitol, the substrate for the ribitol-5-phosphate transferases FKRP and FKTN. Direct use of CDP-ribitol is also effective for matriglycan expression. Ribitol treatment does not alter the expression of FKRP, FKTN as well as LARGEs and ISPD which are critical for the synthesis of matriglycan. The results suggest that alteration in substrates could also be involved in regulation of matriglycan expression. Interestingly, expression of matriglycan is related to cell cycle progression with highest levels in S and G2 phases and ribitol treatment does not alter the pattern. Although matriglycan up-regulation does not affect cell cycle progression and proliferation of the cancer cells tested, the novel substrate-mediated treatment opens a new approach easily applicable to experimental systems in vivo for further exploitation of matriglycan expression in cancer progression and for therapeutic potential. Nature Publishing Group UK 2020-03-18 /pmc/articles/PMC7080755/ /pubmed/32188898 http://dx.doi.org/10.1038/s41598-020-61747-z Text en © The Author(s) 2020 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lu, Pei J.
Tucker, Jason D.
Branch, Elizabeth K.
Guo, Fei
Blaeser, Anthony R.
Lu, Qi L.
Ribitol enhances matriglycan of α-dystroglycan in breast cancer cells without affecting cell growth
title Ribitol enhances matriglycan of α-dystroglycan in breast cancer cells without affecting cell growth
title_full Ribitol enhances matriglycan of α-dystroglycan in breast cancer cells without affecting cell growth
title_fullStr Ribitol enhances matriglycan of α-dystroglycan in breast cancer cells without affecting cell growth
title_full_unstemmed Ribitol enhances matriglycan of α-dystroglycan in breast cancer cells without affecting cell growth
title_short Ribitol enhances matriglycan of α-dystroglycan in breast cancer cells without affecting cell growth
title_sort ribitol enhances matriglycan of α-dystroglycan in breast cancer cells without affecting cell growth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080755/
https://www.ncbi.nlm.nih.gov/pubmed/32188898
http://dx.doi.org/10.1038/s41598-020-61747-z
work_keys_str_mv AT lupeij ribitolenhancesmatriglycanofadystroglycaninbreastcancercellswithoutaffectingcellgrowth
AT tuckerjasond ribitolenhancesmatriglycanofadystroglycaninbreastcancercellswithoutaffectingcellgrowth
AT branchelizabethk ribitolenhancesmatriglycanofadystroglycaninbreastcancercellswithoutaffectingcellgrowth
AT guofei ribitolenhancesmatriglycanofadystroglycaninbreastcancercellswithoutaffectingcellgrowth
AT blaeseranthonyr ribitolenhancesmatriglycanofadystroglycaninbreastcancercellswithoutaffectingcellgrowth
AT luqil ribitolenhancesmatriglycanofadystroglycaninbreastcancercellswithoutaffectingcellgrowth