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Journal of Neuro-Oncology

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01-05-2020 | Adenovirus | Laboratory Investigation

Role of VHL-JAK-STAT signaling pathway in central nervous system hemangioblastoma associated with von Hippel-Lindau disease

Authors: Hiroshi Kanno, Tetsuya Yoshizumi, Masamichi Shinonaga, Atsuhiko Kubo, Hidetoshi Murata, Masahiro Yao

Published in: Journal of Neuro-Oncology | Issue 1/2020

Abstract

Introduction

Central nervous system hemangioblastoma is a benign tumor associated with or without von Hippel-Lindau (VHL) disease which is an autosomal dominant hereditary disease that results from a germline mutation in the VHL gene. A main axis of signaling pathways in central nervous system hemangioblastoma is VHL-HIF signaling pathway. Here, we propose an alternative VHL-JAK-STAT signaling pathway in hemangioblastoma and discuss the role.

Methods

Using MACS method, Scl⁺ hemangioblast-like cells were isolated from multipotent nestin-expressing stem cells. Then, ubiquitination of JAK2 in those cells and immunoprecipitation between JAK2 and VHL were examined. Then, expressions of JAK2 and STAT3 in those cells and expressions of VHL-associated hemangioblastoma tissues were examined. In addition, the VHL genes of patients bearing hemangioblastoma were analyzed.

Results

JAK2 and STAT3 in Scl⁺ hemangioblast-like cells were ubiquitinated after VHL- expression vector was transferred to those cells. Expressions of JAK2 and STAT3 in those cells were well recognized before the transfer, but those disappeared after the transfer. Expressions of both JAK2 and STAT3 in hemangioblastoma tissues were well shown. The VHL gene analysis revealed that patients bearing hemangioblastoma carried missense mutations in 5, small deletions in 2, large deletions in 4, and nonsense mutation in 1

Conclusions

VHL-JAK-STAT signaling pathway might play an important role in proliferation, angiogenesis, and maintenance of stem-cell-nature in hemangioblastoma as an alternative signaling pathway to supplement VHL-HIF signaling pathway.

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Title: Role of VHL-JAK-STAT signaling pathway in central nervous system hemangioblastoma associated with von Hippel-Lindau disease
Authors: Hiroshi Kanno
Tetsuya Yoshizumi
Masamichi Shinonaga
Atsuhiko Kubo
Hidetoshi Murata
Masahiro Yao
Publication date: 01-05-2020
Publisher: Springer US
Keyword: Adenovirus
Published in: Journal of Neuro-Oncology / Issue 1/2020
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-020-03506-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Role of VHL-JAK-STAT signaling pathway in central nervous system hemangioblastoma associated with von Hippel-Lindau disease

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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