Epidermal Growth Factor Receptor Mutation Enhances Expression of Cadherin-5 in Lung Cancer Cells

Hung, Ming‐Szu; Chen, I‐Chuan; Lung, Jrhau; Lin, Paul‐Yann; Li, Ya‐Chin; Tsai, Ying‐Huang

doi:10.1371/journal.pone.0158395

Cited by 28 publications

(26 citation statements)

References 36 publications

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“…In this research, we demonstrated that EGFR enhanced glioma VM formation via increasing the expression levels of VE-cadherin, as well as the expression and activity levels of MMP-2 and MMP-9. Previous studies have shown that EGFR regulates VE-cadherin, MMP-2, and MMP-9 expression and function via the PI3K/AKT pathway, MEK/ERK pathway, and AKT pathway [58, 59]. The present study showed that EGFR increased VE-cadherin expression levels and MMP-2 and MMP-9 expression and activity levels via activating the PI3K/AKT pathway.…”

Section: Discussionsupporting

confidence: 70%

Long Non-Coding RNA HOXA-AS2 Regulates Malignant Glioma Behaviors and Vasculogenic Mimicry Formation via the MiR-373/EGFR Axis

Gao

Liu

et al. 2017

Cell Physiol Biochem

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Background/Aims: Vasculogenic mimicry (VM) has been reported to be a novel glioma neovascularization process. Anti-VM therapy provides new insight into glioma clinical management. In this study, we revealed the role of the long non-coding RNA HOXA cluster antisense RNA 2 (HOXA-AS2) in malignant glioma behaviors and VM formation. Methods: Quantitative real-time PCR was performed to determine the expression levels of HOXA-AS2 in glioma samples and glioblastoma cell lines. CD34-periodic acid-Schiff dual-staining was performed to assess VM in glioma samples. CCK-8, transwell, and Matrigel tube formation assays were performed to measure the effects of HOXA-AS2 knockdown on cell viability, migration, invasion, and VM tube formation, respectively. RNA immunoprecipitation, dual-luciferase reporter and Western blot assays were performed to explore the molecular mechanisms underlying the functions of HOXS-AS2 in glioblastoma cells. A nude mouse xenograft model was used to investigate the role of HOXA-AS2 in xenograft glioma growth and VM density. Student’s t-tests, one-way ANOVAs followed by Bonferroni posthoc tests, and chi-square tests were used for the statistical analyses. Results: HOXA-AS2 was upregulated in glioma samples and cell lines and was positively correlated with VM. HOXA-AS2 knockdown attenuated cell viability, migration, invasion, and VM formation in glioma cells and inhibited the expression of vascular endothelial-cadherin (VE-cadherin), as well as the expression and activity of matrix metalloproteinase matrix metalloproteinase (MMP)-2 and MMP-9. miR-373 was downregulated in glioma samples and cell lines and suppressed malignancy in glioblastoma cells. HOXA-AS2 bound to miR-373 and negatively regulated its expression. Epidermal growth factor receptor (EGFR), a target of miR-373, increased the expression levels of VE-cadherin, as well as the expression and activity levels of MMP-2 and MMP-9, via activating phosphatidylinositol 3-kinase/serine/threonine kinase pathways. HOXA-AS2 knockdown combined with miR-373 overexpression yielded optimal tumor suppressive effects and the lowest VM density in vivo. Conclusion: HOXA-AS2 knockdown inhibited malignant glioma behaviors and VM formation via the miR-373/EGFR axis.

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Section: Discussionsupporting

confidence: 70%

Long Non-Coding RNA HOXA-AS2 Regulates Malignant Glioma Behaviors and Vasculogenic Mimicry Formation via the MiR-373/EGFR Axis

Gao

Liu

et al. 2017

Cell Physiol Biochem

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“…[ 21 ] Besides, another publication has shown an elevated expression of VE-cadherin in lung cancer cells related to increased angiogenesis and metastasis. [ 22 ] We also found that the cancer cells at the invasive front were positive for VE-cadherin [ Figure 4 ]. In addition, VE-cadherin positivity was found in the detached cells, especially around the vessels [ Figure 5 ].…”

Section: Discussionmentioning

confidence: 88%

Expression of vascular endothelial-cadherin in mucoepidermoid carcinoma: Role in cancer development

Irani

Dehghan

2017

J Int Soc Prevent Communit Dent

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Objectives:Mucoepidermoid carcinoma (MEC) accounts for 35% of all malignant salivary gland tumors. Previous investigations have shown that vasculogenic mimicry (VM) exists in many cancers which can be used as a prognostic factor of poor prognosis. Elevated expression level of vascular endothelial (VE)-cadherin has been implicated in cancer neovascularization, growth, and progression. The current study aimed to study the presence of VE-cadherin in VM channels and tumor cells in different grades of MEC.Materials and Methods:A total of 63 MEC samples (21 samples in each grade) were collected from the archive of pathology department of Besat Educational Hospital, Hamadan, Iran, from 2002 to 2016. Hematoxylin and eosin staining was performed to confirm the previous diagnosis. The specimens were then processed for immunohistochemistry analysis. Then, periodic acid–Schiff staining was performed. Analyses were conducted through SPSS software version 22.0 (SPSS, Inc., Chicago, IL, USA). Chi-square test was used to examine the differences between categorical variables. Significance level was set at 0.05. Pearson's correlation was used to assess the co-localization of the marker.Results:A total of 63 samples (35 men; 55.6%, and 28 women; 44.4%) were used for immunohistochemical study. There were statistically significant differences between tumor grade and the expression levels of VE-cadherin (P = 0.000), between tumor grade and VM formation (P = 0.000), and also between tumor grade and microvessel density (MVD) (P = 0.000). Additionally, there was a strong positive correlation between tumor grade and VE-cadherin expression level (Pearson's r = 0.875, P < 0.000).Conclusions:Our results may disclose a definite relationship between VE-cadherin expression level, VM, epithelial–mesenchymal transition, cancer stem cells, and MVD in MEC samples. Thus, it is reasonable to suggest that VE-cadherin is related to angiogenesis and VM formation in MECs.

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“…Interestingly, missense mutations of the EGFR gene are only detected in distally recurrent glioblastoma cases, raising the possibility that EGFR mutation may be related to cellular migration and invasion. EGFR mutations have been reported to be involved in the stimulation of tumor angiogenesis, which is essential to metastasis (49,50). In particular, EGFR mutations have shown to significantly increase cellular migration and invasion via promoting angiogenesis in lung carcinoma cells (50).…”

Section: Discussionmentioning

confidence: 99%

Targeted Genomic Sequencing Reveals Different Evolutionary Patterns Between Locally and Distally Recurrent Glioblastomas

Yoon

Kim

Lee

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: Glioblastoma is the most malignant form of astrocytoma. The purpose of this study was to analyze the genetic characteristics of primary and recurrent glioblastomas using targeted sequencing and investigate the differences in mutational profiles between the locations of tumor recurrence. Materials and Methods: Fourteen glioblastoma patients who developed local (n=10) or distal (n=4) recurrence were included in the study. Targeted sequencing analysis was performed using the primary (n=14) and corresponding recurrent (n=14) tumor tissue samples. Results: The local and distal recurrence groups showed different genetic evolutionary patterns. Most of the locally recurrent glioblastomas demonstrated concordant mutational profiles between the primary and recurrent tumors, suggesting a linear evolution. In contrast, all cases of distally recurrent glioblastomas showed changes in mutational profiles with newly acquired mutations when compared to the corresponding primary tumors, suggesting a branching evolution. Conclusion: Locally and distally recurrent glioblastomas exhibit different evolutionary patterns. Glioblastoma is the most common malignant tumor of the central nervous system (1-9). The current standard treatment for glioblastoma involves surgical resection, followed by concurrent chemoradiation therapy and adjuvant chemotherapy using temozolomide (8-12). Due to the invasive nature of glioblastoma, surgical resection rarely eliminates all tumor cells, and postoperative treatment is usually necessary to prevent disease recurrence. Despite the advances made in therapeutic strategies, the prognosis of patients with glioblastoma remains very poor, with an average survival of 15 months (13-15) and disease recurrence being the major cause of mortality (16-18). Recurrent glioblastomas tend to be more invasive and resistant to chemotherapy than primary tumors. An understanding of the genetic characteristics of recurrent glioblastoma is crucial for identifying potential targets for drug discovery, stratifying patients for diagnosis, and optimizing an effective treatment strategy. Previous studies have shown the molecular features of recurrent glioblastomas. In particular, the mutational profiles observed in recurrent glioblastomas were compared to those of the corresponding primary tumors (19-21). However, there is a lack of studies exploring the differences in mutational profiles between recurrent glioblastomas at different sites (21, 22). In this study, we investigated the mutational profiles of primary and recurrent glioblastomas using 803 This article is freely accessible online.

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Epidermal Growth Factor Receptor Mutation Enhances Expression of Cadherin-5 in Lung Cancer Cells

Cited by 28 publications

References 36 publications

Long Non-Coding RNA HOXA-AS2 Regulates Malignant Glioma Behaviors and Vasculogenic Mimicry Formation via the MiR-373/EGFR Axis

Long Non-Coding RNA HOXA-AS2 Regulates Malignant Glioma Behaviors and Vasculogenic Mimicry Formation via the MiR-373/EGFR Axis

Expression of vascular endothelial-cadherin in mucoepidermoid carcinoma: Role in cancer development

Targeted Genomic Sequencing Reveals Different Evolutionary Patterns Between Locally and Distally Recurrent Glioblastomas

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