Cancer Malignancy Is Correlated with Upregulation of PCYT2-Mediated Glycerol Phosphate Modification of α-Dystroglycan
The dystrophin–glycoprotein complex connects the cytoskeleton with base membrane components such as laminin through unique O-glycans displayed on α-dystroglycan (α-DG). Genetic impairment of elongation of these glycans causes congenital muscular dystrophies. We previously identified that glycerol ph...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223686/ https://www.ncbi.nlm.nih.gov/pubmed/35743105 http://dx.doi.org/10.3390/ijms23126662 |
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author | Umezawa, Fumiko Natsume, Makoto Fukusada, Shigeki Nakajima, Kazuki Yamasaki, Fumiya Kawashima, Hiroto Kuo, Chu-Wei Khoo, Kay-Hooi Shimura, Takaya Yagi, Hirokazu Kato, Koichi |
author_facet | Umezawa, Fumiko Natsume, Makoto Fukusada, Shigeki Nakajima, Kazuki Yamasaki, Fumiya Kawashima, Hiroto Kuo, Chu-Wei Khoo, Kay-Hooi Shimura, Takaya Yagi, Hirokazu Kato, Koichi |
author_sort | Umezawa, Fumiko |
collection | PubMed |
description | The dystrophin–glycoprotein complex connects the cytoskeleton with base membrane components such as laminin through unique O-glycans displayed on α-dystroglycan (α-DG). Genetic impairment of elongation of these glycans causes congenital muscular dystrophies. We previously identified that glycerol phosphate (GroP) can cap the core part of the α-DG O-glycans and terminate their further elongation. This study examined the possible roles of the GroP modification in cancer malignancy, focusing on colorectal cancer. We found that the GroP modification critically depends on PCYT2, which serves as cytidine 5′-diphosphate-glycerol (CDP-Gro) synthase. Furthermore, we identified a significant positive correlation between cancer progression and GroP modification, which also correlated positively with PCYT2 expression. Moreover, we demonstrate that GroP modification promotes the migration of cancer cells. Based on these findings, we propose that the GroP modification by PCYT2 disrupts the glycan-mediated cell adhesion to the extracellular matrix and thereby enhances cancer metastasis. Thus, the present study suggests the possibility of novel approaches for cancer treatment by targeting the PCYT2-mediated GroP modification. |
format | Online Article Text |
id | pubmed-9223686 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92236862022-06-24 Cancer Malignancy Is Correlated with Upregulation of PCYT2-Mediated Glycerol Phosphate Modification of α-Dystroglycan Umezawa, Fumiko Natsume, Makoto Fukusada, Shigeki Nakajima, Kazuki Yamasaki, Fumiya Kawashima, Hiroto Kuo, Chu-Wei Khoo, Kay-Hooi Shimura, Takaya Yagi, Hirokazu Kato, Koichi Int J Mol Sci Article The dystrophin–glycoprotein complex connects the cytoskeleton with base membrane components such as laminin through unique O-glycans displayed on α-dystroglycan (α-DG). Genetic impairment of elongation of these glycans causes congenital muscular dystrophies. We previously identified that glycerol phosphate (GroP) can cap the core part of the α-DG O-glycans and terminate their further elongation. This study examined the possible roles of the GroP modification in cancer malignancy, focusing on colorectal cancer. We found that the GroP modification critically depends on PCYT2, which serves as cytidine 5′-diphosphate-glycerol (CDP-Gro) synthase. Furthermore, we identified a significant positive correlation between cancer progression and GroP modification, which also correlated positively with PCYT2 expression. Moreover, we demonstrate that GroP modification promotes the migration of cancer cells. Based on these findings, we propose that the GroP modification by PCYT2 disrupts the glycan-mediated cell adhesion to the extracellular matrix and thereby enhances cancer metastasis. Thus, the present study suggests the possibility of novel approaches for cancer treatment by targeting the PCYT2-mediated GroP modification. MDPI 2022-06-15 /pmc/articles/PMC9223686/ /pubmed/35743105 http://dx.doi.org/10.3390/ijms23126662 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Umezawa, Fumiko Natsume, Makoto Fukusada, Shigeki Nakajima, Kazuki Yamasaki, Fumiya Kawashima, Hiroto Kuo, Chu-Wei Khoo, Kay-Hooi Shimura, Takaya Yagi, Hirokazu Kato, Koichi Cancer Malignancy Is Correlated with Upregulation of PCYT2-Mediated Glycerol Phosphate Modification of α-Dystroglycan |
title | Cancer Malignancy Is Correlated with Upregulation of PCYT2-Mediated Glycerol Phosphate Modification of α-Dystroglycan |
title_full | Cancer Malignancy Is Correlated with Upregulation of PCYT2-Mediated Glycerol Phosphate Modification of α-Dystroglycan |
title_fullStr | Cancer Malignancy Is Correlated with Upregulation of PCYT2-Mediated Glycerol Phosphate Modification of α-Dystroglycan |
title_full_unstemmed | Cancer Malignancy Is Correlated with Upregulation of PCYT2-Mediated Glycerol Phosphate Modification of α-Dystroglycan |
title_short | Cancer Malignancy Is Correlated with Upregulation of PCYT2-Mediated Glycerol Phosphate Modification of α-Dystroglycan |
title_sort | cancer malignancy is correlated with upregulation of pcyt2-mediated glycerol phosphate modification of α-dystroglycan |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223686/ https://www.ncbi.nlm.nih.gov/pubmed/35743105 http://dx.doi.org/10.3390/ijms23126662 |
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