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The prognostic value of Tiam1 correlates with its roles in epithelial–mesenchymal transition progression and angiogenesis in lung adenocarcinoma
BACKGROUND: Tiam1 has been identified as an oncogene and acts as an activator of GTPase Rac. Tiam1 was reported to be a promoter of cancer progression in various cancer types, while in lung adenocarcinoma, its mechanism of action is poorly understood. MATERIALS AND METHODS: Immunohistochemistry stai...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388966/ https://www.ncbi.nlm.nih.gov/pubmed/30863182 http://dx.doi.org/10.2147/CMAR.S195093 |
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author | Zhu, Guang Zhang, Yuan Wang, Qianrong Che, Shuanlong Yang, Yang Chen, Liyan Lin, Zhenhua |
author_facet | Zhu, Guang Zhang, Yuan Wang, Qianrong Che, Shuanlong Yang, Yang Chen, Liyan Lin, Zhenhua |
author_sort | Zhu, Guang |
collection | PubMed |
description | BACKGROUND: Tiam1 has been identified as an oncogene and acts as an activator of GTPase Rac. Tiam1 was reported to be a promoter of cancer progression in various cancer types, while in lung adenocarcinoma, its mechanism of action is poorly understood. MATERIALS AND METHODS: Immunohistochemistry staining and Western blot assay were used to determine Tiam1 expression in lung adenocarcinoma tissues, and its association with prognosis was determined by statistical analysis. We depleted Tiam1 in both A549 and H1975 cancer cell lines. Carboxyfluorescein diacetate succinimidyl ester staining and colony formation assays were used to evaluate its impact on cell proliferation ability after depletion. Transwell migration assay and wound healing assays were performed to determine its impact on migration ability of both cell lines. Western blot assay and immunofluorescence staining were used to analyze the association between Tiam1 and epithelial–mesenchymal transition (EMT) progression. Tube formation assay and vasculogenic mimicry assay were used to show the impact of Tiam1 depletion on cancer angiogenesis. RESULTS: In this study, we demonstrated that Tiam1 overexpression in lung adenocarcinoma was significantly associated with advanced tumor grade and poor prognosis. In vitro assays indicated that Tiam1 depletion significantly inhibited cell proliferation, colony formation, and migration capacities in A549 and H1975 cells. Further investigations revealed that Tiam1 plays an important role in EMT program enhancement, angiogenesis, and accelerated tumor progression. Notably, Tiam1 depletion in cancer cells strongly inhibited human umbilical vein endothelial cell angiogenesis and vasculogenic mimicry capacities of both cancer cell lines. CONCLUSION: Tiam1 overexpression is associated with lung adenocarcinoma progression and may indicate poor prognosis. Tiam1 accelerated tumor progression due to EMT and angiogenesis enhancement. Our data may provide a novel therapeutic target for lung adenocarcinoma. |
format | Online Article Text |
id | pubmed-6388966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-63889662019-03-12 The prognostic value of Tiam1 correlates with its roles in epithelial–mesenchymal transition progression and angiogenesis in lung adenocarcinoma Zhu, Guang Zhang, Yuan Wang, Qianrong Che, Shuanlong Yang, Yang Chen, Liyan Lin, Zhenhua Cancer Manag Res Original Research BACKGROUND: Tiam1 has been identified as an oncogene and acts as an activator of GTPase Rac. Tiam1 was reported to be a promoter of cancer progression in various cancer types, while in lung adenocarcinoma, its mechanism of action is poorly understood. MATERIALS AND METHODS: Immunohistochemistry staining and Western blot assay were used to determine Tiam1 expression in lung adenocarcinoma tissues, and its association with prognosis was determined by statistical analysis. We depleted Tiam1 in both A549 and H1975 cancer cell lines. Carboxyfluorescein diacetate succinimidyl ester staining and colony formation assays were used to evaluate its impact on cell proliferation ability after depletion. Transwell migration assay and wound healing assays were performed to determine its impact on migration ability of both cell lines. Western blot assay and immunofluorescence staining were used to analyze the association between Tiam1 and epithelial–mesenchymal transition (EMT) progression. Tube formation assay and vasculogenic mimicry assay were used to show the impact of Tiam1 depletion on cancer angiogenesis. RESULTS: In this study, we demonstrated that Tiam1 overexpression in lung adenocarcinoma was significantly associated with advanced tumor grade and poor prognosis. In vitro assays indicated that Tiam1 depletion significantly inhibited cell proliferation, colony formation, and migration capacities in A549 and H1975 cells. Further investigations revealed that Tiam1 plays an important role in EMT program enhancement, angiogenesis, and accelerated tumor progression. Notably, Tiam1 depletion in cancer cells strongly inhibited human umbilical vein endothelial cell angiogenesis and vasculogenic mimicry capacities of both cancer cell lines. CONCLUSION: Tiam1 overexpression is associated with lung adenocarcinoma progression and may indicate poor prognosis. Tiam1 accelerated tumor progression due to EMT and angiogenesis enhancement. Our data may provide a novel therapeutic target for lung adenocarcinoma. Dove Medical Press 2019-02-21 /pmc/articles/PMC6388966/ /pubmed/30863182 http://dx.doi.org/10.2147/CMAR.S195093 Text en © 2019 Zhu et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Zhu, Guang Zhang, Yuan Wang, Qianrong Che, Shuanlong Yang, Yang Chen, Liyan Lin, Zhenhua The prognostic value of Tiam1 correlates with its roles in epithelial–mesenchymal transition progression and angiogenesis in lung adenocarcinoma |
title | The prognostic value of Tiam1 correlates with its roles in epithelial–mesenchymal transition progression and angiogenesis in lung adenocarcinoma |
title_full | The prognostic value of Tiam1 correlates with its roles in epithelial–mesenchymal transition progression and angiogenesis in lung adenocarcinoma |
title_fullStr | The prognostic value of Tiam1 correlates with its roles in epithelial–mesenchymal transition progression and angiogenesis in lung adenocarcinoma |
title_full_unstemmed | The prognostic value of Tiam1 correlates with its roles in epithelial–mesenchymal transition progression and angiogenesis in lung adenocarcinoma |
title_short | The prognostic value of Tiam1 correlates with its roles in epithelial–mesenchymal transition progression and angiogenesis in lung adenocarcinoma |
title_sort | prognostic value of tiam1 correlates with its roles in epithelial–mesenchymal transition progression and angiogenesis in lung adenocarcinoma |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388966/ https://www.ncbi.nlm.nih.gov/pubmed/30863182 http://dx.doi.org/10.2147/CMAR.S195093 |
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