FAM20B Gain-of-Function Blocks the Synthesis of Glycosaminoglycan Chains of Proteoglycans and Inhibits Proliferation and Migration of Glioblastoma Cells
Heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans (PGs) are essential regulators of many biological processes including cell differentiation, signalization, and proliferation. PGs interact mainly via their glycosaminoglycan (GAG) chains, with a large number of ligands including growth...
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2025-05-01
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| author | Lydia Barré Irfan Shaukat Mohamed Ouzzine |
| author_facet | Lydia Barré Irfan Shaukat Mohamed Ouzzine |
| author_sort | Lydia Barré |
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| description | Heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans (PGs) are essential regulators of many biological processes including cell differentiation, signalization, and proliferation. PGs interact mainly via their glycosaminoglycan (GAG) chains, with a large number of ligands including growth factors, enzymes, and extracellular matrix components, thereby modulating their biological activities. HSPGs and CSPGs share a common tetrasaccharide linker region, which undergoes modifications, particularly the phosphorylation of the xylose residue by the kinase FAM20B. Here, we demonstrated that <i>FAM20B</i> gain-of-function decreased, in a dose dependent manner, the synthesis of both CS- and HS-attached PGs. In addition, we showed that blockage of GAG chain synthesis by FAM20B was suppressed by the mutation of aspartic acid residues D289 and D309 of the catalytic domain. Interestingly, we bring evidence that, in contrast to FAM20B, expression of the 2-phosphoxylose phosphatase XYLP increases, in a dose dependent manner, GAG chain synthesis and rescues the blockage of GAG chains synthesis induced by FAM20B. In line with previous reports, we found that <i>FAM20B</i> loss-of-function reduced GAG chain synthesis. Finally, we found that FAM20B inhibited proliferation and migration of glioblastoma cells, thus revealing the critical role of GAG chains of PGs in glioblastoma cell tumorigenesis. This study revealed that both gain- and loss-of-function of <i>FAM20B</i> led to decreased GAG chain synthesis, therefore suggesting that a balance between phosphorylation and dephosphorylation of the xylose by FAM20B and XYLP, respectively, is probably an essential factor for the regulation of the rate of PG synthesis. |
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| institution | Kabale University |
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| publishDate | 2025-05-01 |
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| spelling | doaj-art-bb53f638315541748743dbf1ddfb99302025-08-20T03:47:53ZengMDPI AGCells2073-44092025-05-01141071210.3390/cells14100712FAM20B Gain-of-Function Blocks the Synthesis of Glycosaminoglycan Chains of Proteoglycans and Inhibits Proliferation and Migration of Glioblastoma CellsLydia Barré0Irfan Shaukat1Mohamed Ouzzine2UMR7365 CNRS-Université de Lorraine, Biopôle, Faculté de Médecine, CS 50184, 54505 Vandoeuvre-lès-Nancy Cedex, FranceUMR7365 CNRS-Université de Lorraine, Biopôle, Faculté de Médecine, CS 50184, 54505 Vandoeuvre-lès-Nancy Cedex, FranceUMR7365 CNRS-Université de Lorraine, Biopôle, Faculté de Médecine, CS 50184, 54505 Vandoeuvre-lès-Nancy Cedex, FranceHeparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans (PGs) are essential regulators of many biological processes including cell differentiation, signalization, and proliferation. PGs interact mainly via their glycosaminoglycan (GAG) chains, with a large number of ligands including growth factors, enzymes, and extracellular matrix components, thereby modulating their biological activities. HSPGs and CSPGs share a common tetrasaccharide linker region, which undergoes modifications, particularly the phosphorylation of the xylose residue by the kinase FAM20B. Here, we demonstrated that <i>FAM20B</i> gain-of-function decreased, in a dose dependent manner, the synthesis of both CS- and HS-attached PGs. In addition, we showed that blockage of GAG chain synthesis by FAM20B was suppressed by the mutation of aspartic acid residues D289 and D309 of the catalytic domain. Interestingly, we bring evidence that, in contrast to FAM20B, expression of the 2-phosphoxylose phosphatase XYLP increases, in a dose dependent manner, GAG chain synthesis and rescues the blockage of GAG chains synthesis induced by FAM20B. In line with previous reports, we found that <i>FAM20B</i> loss-of-function reduced GAG chain synthesis. Finally, we found that FAM20B inhibited proliferation and migration of glioblastoma cells, thus revealing the critical role of GAG chains of PGs in glioblastoma cell tumorigenesis. This study revealed that both gain- and loss-of-function of <i>FAM20B</i> led to decreased GAG chain synthesis, therefore suggesting that a balance between phosphorylation and dephosphorylation of the xylose by FAM20B and XYLP, respectively, is probably an essential factor for the regulation of the rate of PG synthesis.https://www.mdpi.com/2073-4409/14/10/712FAM20Bproteoglycansglycosaminoglycan synthesisglioblastoma |
| spellingShingle | Lydia Barré Irfan Shaukat Mohamed Ouzzine FAM20B Gain-of-Function Blocks the Synthesis of Glycosaminoglycan Chains of Proteoglycans and Inhibits Proliferation and Migration of Glioblastoma Cells Cells FAM20B proteoglycans glycosaminoglycan synthesis glioblastoma |
| title | FAM20B Gain-of-Function Blocks the Synthesis of Glycosaminoglycan Chains of Proteoglycans and Inhibits Proliferation and Migration of Glioblastoma Cells |
| title_full | FAM20B Gain-of-Function Blocks the Synthesis of Glycosaminoglycan Chains of Proteoglycans and Inhibits Proliferation and Migration of Glioblastoma Cells |
| title_fullStr | FAM20B Gain-of-Function Blocks the Synthesis of Glycosaminoglycan Chains of Proteoglycans and Inhibits Proliferation and Migration of Glioblastoma Cells |
| title_full_unstemmed | FAM20B Gain-of-Function Blocks the Synthesis of Glycosaminoglycan Chains of Proteoglycans and Inhibits Proliferation and Migration of Glioblastoma Cells |
| title_short | FAM20B Gain-of-Function Blocks the Synthesis of Glycosaminoglycan Chains of Proteoglycans and Inhibits Proliferation and Migration of Glioblastoma Cells |
| title_sort | fam20b gain of function blocks the synthesis of glycosaminoglycan chains of proteoglycans and inhibits proliferation and migration of glioblastoma cells |
| topic | FAM20B proteoglycans glycosaminoglycan synthesis glioblastoma |
| url | https://www.mdpi.com/2073-4409/14/10/712 |
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