Prognostic implications of ezrin and phosphorylated ezrin expression in non-small cell lung cancer

Jin, Tiefeng; Jin, Jingchun; Li, Xiangyu; Zhang, Songnan; Choi, Yun Ho; Piao, Yingshi; Shen, Xionghu; Lin, Zhenhua

doi:10.1186/1471-2407-14-191

Cited by 30 publications

(21 citation statements)

References 30 publications

(41 reference statements)

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“…In addition, it was also found that adenovirus-mediated siRNA targetting ezrin inhibits the proliferation, migration, and invasion of MG-63 cells, impedes cell cycle progression and induces apoptosis of MG-63 cells. As a cross-linker between the plasma membrane and actin cytoskeleton, ezrin participated in cell motility, membrane trafficking, as well as cell adhesion and apoptosis [ 29 ]. Bulut et al [ 30 ] demonstrated that ezrin can inhibit invasion by small molecule inhibitors to osteosarcoma cells.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated small interfering RNA targeting ezrin induces apoptosis and inhibits metastasis of human osteosarcoma MG-63 cells

Zhou

Zou

2018

Bioscience Reports

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Osteosarcoma is a disease prone to recurrence and metastasis, and adenovirus expression vector is frequently studied as a therapeutic target of osteosarcoma in recent years. The present study attempts to explore the effect of adenovirus-mediated siRNA targetting ezrin on the proliferation, migration, invasion, and apoptosis of human osteosarcoma MG-63 cells. Human osteosarcoma MG-63 cell line was selected for construction of recombinant adenovirus vector. The mRNA and protein levels of ezrin, Bcl2-associated X protein (Bax), B cell lymphoma-2 (Bcl-2), p21, p53, Caspase-3, matrix metalloproteinase (MMP) 2 (MMP-2) and MMP-9, Cyclin D1, and cyclin-dependent kinase 4a (CDK4a) were determined. Through ELISA, the levels of Caspase-3, MMP-2 and MMP-9 were examined. Finally, human osteosarcoma MG-63 cell viability, growth, invasion, migration, and apoptosis were detected. Initially, adenovirus expression vector of ezrin was constructed by ezrin 2 siRNA sequence. Adenovirus-mediated siRNA targetting ezrin reduced expression of ezrin in MG-63 cells. The results revealed that adenovirus-mediated siRNA targetting ezrin elevated expression levels of Bax, p21, p53, and Caspase-3, Cyclin D1, and CDK4a and reduced expression levels of Bcl-2, MMP-2 and MMP-9. Furthermore, adenovirus-mediated siRNA targetting ezrin inhibited human osteosarcoma MG-63 cell viability, growth, invasion, and migration, and promoted apoptosis. Our study demonstrates that adenovirus-mediated siRNA targetting ezrin can induce apoptosis and inhibit the proliferation, migration, and invasion of human osteosarcoma MG-63 cells.

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Section: Discussionmentioning

confidence: 99%

Adenovirus-mediated small interfering RNA targeting ezrin induces apoptosis and inhibits metastasis of human osteosarcoma MG-63 cells

Zhou

Zou

2018

Bioscience Reports

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“…We found that the levels of AJAP1 mRNA correlated significantly with those of EZR in ESCC and FHs74 cell lines. EZR is a member of the ezrin-radixin-moesin family and acts as a cross-linker between the plasma membrane and the actin cytoskeleton (34). Inactive EZR is located in the cytoplasm, and its C-terminal domain, an F-actin-binding site, is masked by the EZR N-terminal domain or those of other ERM proteins (35).…”

Section: Discussionmentioning

confidence: 99%

Adherens junctions associated protein 1 serves as a predictor of recurrence of squamous cell carcinoma of the esophagus

Tanaka

Kanda

Koike

et al. 2015

International Journal of Oncology

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Esophageal squamous cell carcinoma (ESCC), the most common esophageal cancer in East Asia, is among the six cancers with the highest fatality rates worldwide. Unfortunately, multidisciplinary treatment strategies have not achieved satisfactory outcomes. Therefore, novel insights into the molecular biology of ESCC are required to improve treatment. The gene encoding the transmembrane adherens junctions-associated protein-1 (AJAP1) expressed by epithelial cells resides in chromosome 1p36, which is frequently lost or epigenetically silenced in several malignancies. Here, we investigated the expression levels and regulatory mechanism of AJAP1 transcription. We determined the levels of AJAP1 mRNA and the genes encoding potentially interacting proteins expressed by ESCC cell lines, as well as the chromosomal copy number of AJAP1 and the methylation status of its promoter region. AJAP1 mRNA levels of 78 pairs of surgically resected specimens were determined to evaluate the association of AJAP1 expression and clinicopathological factors. Nine ESCC cell lines differentially expressed AJAP1 mRNA, and demethylation of hypermethylated AJAP1 genomic DNA reactivated AJAP1 mRNA expression. The copy number of sequences upstream or downstream of the AJAP1 transcriptional start site was not detectably altered. AJAP1 mRNA levels correlated inversely with those of ezrin (EZR) and were significantly lower in ESCC tissues compared with adjacent normal tissues. AJAP1 mRNA levels decreased gradually with increasing tumor stage. Patients with downregulated AJAP1 transcription were more likely to experience shorter overall and disease-free survival. Multivariate analysis of disease-free survival identified downregulated AJAP1 transcription as an independent prognostic factor. These results suggest that in ESCC, AJAP1 acts as a putative tumor suppressor and that AJAP1 transcription is regulated by promoter hypermethylation. These findings indicate that downregulated AJAP1 transcription may serve as a novel tumor biomarker to predict recurrence of ESCC after esophagectomy.

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“…Despite progress in the multimodality treatment of lung cancer, prognosis is still poor, with 10-15% 5-year survival rates. More than 90% of deaths from NSCLC are attributable to metastases [ 1 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

NQO1 protein expression predicts poor prognosis of non-small cell lung cancers

Zhang

Jin

et al. 2015

BMC Cancer

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BackgroundHigh-level expression of NAD(P)H: quinoneoxidoreductase 1 (NQO1) has been correlated with many types of human cancers, suggesting that NQO1 plays important roles in tumor occurrence and progression. This study attempted to explore the role of NQO1 in tumor progression and prognostic evaluation of non-small cell lung cancer (NSCLC).MethodsTotal 164 tissue samples, including 150 NSCLC paired with the adjacent non-tumor tissues and 14 normal lung tissues, were picked-up for immunohistochemical (IHC) staining of the NQO1 protein, and immunofluorescence (IF) staining was also performed to detect the subcellular localization of the NQO1 protein in A549 human lung cancer cells. The correlation between NQO1 expression and clinicopathological characteristics were evaluated by Chi-square test and Fisher’s exact tests. The disease-free survival (DFS) and overall survival (OS) rates of NSCLC patients were calculated by the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model.ResultsThe NQO1 protein showed a mainly cytoplasmic staining pattern in lung cancer cells, including adenocarcinoma and squamous cell carcinoma (SCC). Both positive rate and strongly positive rate of NQO1 protein expression were significantly higher in NSCLC (59.3% and 28.0%) than that in adjacent non tumor (8.0% and 1.3%) and normal lung tissues (0%). The positive rate of NQO1 was related with clinical stage and lymph node metastasis, and the strongly positive rate of NQO1 protein was significantly correlated with tumor size, poor differentiation, advanced clinical stage and lymph node metastasis in NSCLC. Additionally, survival analyses showed that the patients with NQO1 positive expression had lower OS rates compared with those with NQO1 negative expression in the groups of T1-2, T3-4, without LN metastasis and stage I-II of NSCLC, respectively; however, in the groups of patients with LN metastasis or III-IV stages, OS rate was not correlated with NQO1 expression status. Moreover, multivariate analysis suggested that NQO1 emerged as a significant independent prognostic factor along with tumor size, differentiation, lymph node metastasis and clinical stage in patients with NSCLC.ConclusionsNQO1 is upregulated in NSCLC, and it may be a useful poor prognostic biomarker and a potential therapeutic target for patients with NSCLC.

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Prognostic implications of ezrin and phosphorylated ezrin expression in non-small cell lung cancer

Cited by 30 publications

References 30 publications

Adenovirus-mediated small interfering RNA targeting ezrin induces apoptosis and inhibits metastasis of human osteosarcoma MG-63 cells

Adenovirus-mediated small interfering RNA targeting ezrin induces apoptosis and inhibits metastasis of human osteosarcoma MG-63 cells

Adherens junctions associated protein 1 serves as a predictor of recurrence of squamous cell carcinoma of the esophagus

NQO1 protein expression predicts poor prognosis of non-small cell lung cancers

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