AJAP1 is Dysregulated at an Early Stage of Gliomagenesis and Suppresses Invasion Through Cytoskeleton Reorganization

Abstract

SUMMARY Aims 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.

MiR‐552 promotes the proliferation, migration and EMT of hepatocellular carcinoma cells by inhibiting AJAP1 expression

“…In addition, the tumour development in our mouse model supported the in vitro results. As was demonstrated by Han et al, AJAP1 overexpression in vitro functioned similarly to in vivo overexpression in glioma cell lines. Furthermore, Ezaka et al proved that AJAP1 levels were inversely correlated with the levels of SRC in HCC cell lines and tissues, which verified our hypothesis shown in Figure .…”

Reduced Expression of Adherens Junctions Associated Protein 1 Predicts Recurrence of Hepatocellular Carcinoma After Curative Hepatectomy

“…35,36 These findings, taken together with evidence described above indicating that AJAP1 is a tumor suppressor, led us to investigate AJAP1 expression in patients with HCC and to determine its regulatory mechanism.…”

“…42,43 AJAP1 may interact with the E-cadherin-catenin complex and CD147. 35,36 In the present study, we determined the expression of HCC-related cell adhesion molecules to identify novel genes whose products may interact with AJAP1 in HCC cells. We discovered significant correlations between the levels of AJAP1 and SRC mRNAs in HCC cell lines and in surgically resected tissues.…”

Endogenous AJAP1 associates with the cytoskeleton and attenuates angiogenesis in endothelial cells

“…AJAP1 has been reported to be involved in important cellular processes such as cell migration and invasion by modulating adherens junctions and remodeling of the ECM and the cytoskeleton (Gross et al, 2009; Schreiner et al, 2007; Han et al, 2014). …”