Pancreatic endoplasmic reticulum kinase activation promotes medulloblastoma cell migration and invasion through induction of vascular endothelial growth factor A

PloS One
Stephanie JamisonWensheng Lin

Abstract

Evidence is accumulating that activation of the pancreatic endoplasmic reticulum kinase (PERK) in response to endoplasmic reticulum (ER) stress adapts tumor cells to the tumor microenvironment and enhances tumor angiogenesis by inducing vascular endothelial growth factor A (VEGF-A). Recent studies suggest that VEGF-A can act directly on certain tumor cell types in an autocrine manner, via binding to VEGF receptor 2 (VEGFR2), to promote tumor cell migration and invasion. Although several reports show that PERK activation increases VEGF-A expression in medulloblastoma, the most common solid malignancy of childhood, the role that either PERK or VEGF-A plays in medulloblastoma remains elusive. In this study, we mimicked the moderate enhancement of PERK activity observed in tumor patients using a genetic approach and a pharmacologic approach, and found that moderate activation of PERK signaling facilitated medulloblastoma cell migration and invasion and increased the production of VEGF-A. Moreover, using the VEGFR2 inhibitor SU5416 and the VEGF-A neutralizing antibody to block VEGF-A/VEGFR2 signaling, our results suggested that tumor cell-derived VEGF-A promoted medulloblastoma cell migration and invasion through VEGFR2 signaling, a...Continue Reading

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Citations

Dec 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Qiujing YuSerge Y Fuchs
Mar 27, 2016·Brain Research·Pierre-Jean Le ResteEric Chevet
Jul 1, 2016·Brain Research·Pierre-Jean Le ResteEric Chevet
Feb 7, 2018·Frontiers in Microbiology·Paula DíazAndrew F G Quest
Nov 2, 2016·Oncotarget·Sarrabeth StoneWensheng Lin
Jan 5, 2019·Journal of breast cancer·Chang-Chang Han, Fu-Sheng Wan
Feb 3, 2019·Journal of Neuroinflammation·Yuan YueWensheng Lin
Mar 16, 2021·Frontiers in Cell and Developmental Biology·Paula DíazSergio Lavandero
Apr 23, 2021·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Marcela de Oliveira SilvaMaría Sol Brassesco

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Methods Mentioned

BETA
Protein Assay
Assay
PCR
ELISA
transgenic

Software Mentioned

NIH Image J
NIH ImageJ
Sigmaplot
SUnSET

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