AJAP1 is dysregulated at an early stage of gliomagenesis and suppresses invasion through cytoskeleton reorganization.
OBJECTIVE
Down-regulation of AJAP1 in glioblastoma multiforme (GBM) has been reported. However, the expression profiles of AJAP1 in gliomas and the underlying mechanisms of AJAP1 function on invasion are still poorly understood.


METHODS
The gene profiles of AJAP1 in glioma patients were studied among four independent cohorts. Confocal imaging was used to analyze the AJAP1 localization. After AJAP1 overexpression in GBM cell lines, cellular polarity, cytoskeleton distribution, and antitumor effect were investigated in vitro and in vivo.


RESULTS
AJAP1 expression was significantly decreased in gliomas compared with normal brain in REMBRANDT and CGCA cohorts. Additionally, low AJAP1 expression was associated with worse survival in GBMs in REMBRANDT and TCGA U133A cohorts and was significantly associated with classical and mesenchymal subtypes of GBMs among four cohorts. Confocal imaging indicated AJAP1 localized in cell membranes in low-grade gliomas and AJAP1-overexpressing GBM cells, but difficult to assess in high-grade gliomas due to its absence. AJAP1 overexpression altered the cytoskeleton and cellular polarity in vitro and inhibited the tumor growth in vivo.


CONCLUSIONS
AJAP1 is dysregulated at an early stage of gliomagenesis and may suppress glioma cell invasion and proliferation, which suggests that AJAP1 may be a potential diagnostic and prognostic marker for gliomas.
Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China; Tianjin Neurological Institute, Tianjin, China; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China.
Lei
L
Han
Kai-Liang
KL
Zhang
Jun-Xia
JX
Zhang
Liang
L
Zeng
Chun-Hui
CH
Di
Brian E
BE
Fee
Miriam
M
Rivas
Zhao-Shi
ZS
Bao
Tao
T
Jiang
Darrell
D
Bigner
Chun-Sheng
CS
Kang
David Cory
DC
Adamson
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D015331:Cohort Studies; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D018450:Disease Progression; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation
C483313:AJAP1 protein, human; D015815:Cell Adhesion Molecules
AJAP1; Cytoskeleton; Glioma; Invasion; Proliferation