Brain-specific glycosylation enzyme GnT-IX maintains levels of protein tyrosine phosphatase receptor PTPRZ, thereby mediating glioma growth.

Autor:	Nagai K; Department of Neurosurgery, Fukushima Medical University, Fukushima, Japan., Muto Y; Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan., Miura S; Department of Clinical Laboratory Sciences, School of Health Sciences, Fukushima Medical University, Fukushima, Japan., Takahashi K; Department of Clinical Laboratory Sciences, School of Health Sciences, Fukushima Medical University, Fukushima, Japan., Naruse Y; Department of Neurosurgery, Fukushima Medical University, Fukushima, Japan., Hiruta R; Department of Neurosurgery, Fukushima Medical University, Fukushima, Japan., Hashimoto Y; Department of Diagnostic Pathology, Fukushima Medical University, Fukushima, Japan., Uzuki M; Department of Clinical Laboratory Sciences, School of Health Sciences, Fukushima Medical University, Fukushima, Japan., Haga Y; Cancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan., Fujii R; Cancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan., Ueda K; Cancer Proteomics Group, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan., Kawaguchi Y; Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Research Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan., Fujii M; Department of Neurosurgery, Fukushima Medical University, Fukushima, Japan. Electronic address: fujii@fmu.ac.jp., Kitazume S; Department of Clinical Laboratory Sciences, School of Health Sciences, Fukushima Medical University, Fukushima, Japan. Electronic address: shinobuk@fmu.ac.jp.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2023 Sep; Vol. 299 (9), pp. 105128. Date of Electronic Publication: 2023 Aug 04.
DOI:	10.1016/j.jbc.2023.105128
Abstrakt:	Gliomas are the most prevalent primary tumor of the central nervous system. Despite advances in imaging technologies, neurosurgical techniques, and radiotherapy, a cure for high-grade glioma remains elusive. Several groups have reported that protein tyrosine phosphatase receptor type Z (PTPRZ) is highly expressed in glioblastoma, and that targeting PTPRZ attenuates tumor growth in mice. PTPRZ is modified with diverse glycan, including the PTPRZ-unique human natural killer-1 capped O-mannosyl core M2 glycans. However, the regulation and function of these unique glycans are unclear. Using CRISPR genome-editing technology, we first demonstrated that disruption of the PTPRZ gene in human glioma LN-229 cells resulted in profoundly reduced tumor growth in xenografted mice, confirming the potential of PTPRZ as a therapeutic target for glioma. Furthermore, multiple glycan analyses revealed that PTPRZ derived from glioma patients and from xenografted glioma expressed abundant levels of human natural killer-1-capped O-Man glycans via extrinsic signals. Finally, since deficiency of O-Man core M2 branching enzyme N-acetylglucosaminyltransferase IX (GnT-IX) was reported to reduce PTPRZ protein levels, we disrupted the GnT-IX gene in LN-229 cells and found a significant reduction of glioma growth both in vitro and in the xenograft model. These results suggest that the PTPR glycosylation enzyme GnT-IX may represent a promising therapeutic target for glioma. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu