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The prognostic value of Tiam1 correlates with its roles in epithelial–mesenchymal transition progression and angiogenesis in lung adenocarcinoma

Authors Zhu G, Zhang Y, Wang Q, Che S, Yang Y, Chen L, Lin Z

Received 18 November 2018

Accepted for publication 21 January 2019

Published 21 February 2019 Volume 2019:11 Pages 1741—1752

DOI https://doi.org/10.2147/CMAR.S195093

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Justinn Cochran

Peer reviewer comments 2

Editor who approved publication: Dr Kenan Onel


Guang Zhu,1,2 Yuan Zhang,1,2 Qianrong Wang,1,2 Shuanlong Che,1,2 Yang Yang,1,2 Liyan Chen,1,2 Zhenhua Lin1,2

1Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji 133002, China; 2Key Laboratory of the Science and Technology Department of Jilin Province, Yanji 133002, China

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.

Keywords: Tiam1, prognostic value, EMT, angiogenesis, VM, lung adenocarcinoma

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