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Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | Metastasis | Primary research

Upregulation of ARHGAP30 attenuates pancreatic cancer progression by inactivating the β-catenin pathway

Authors: Yongping Zhou, Zhiyuan Hua, Ye Zhu, Liying Wang, Fangming Chen, Ting Shan, Yunhai Zhou, Tu Dai

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Pancreatic cancer is a highly malignant gastrointestinal cancer that can widely metastasize during the early stage of disease, and it is associated with one of the worst prognoses among cancers. In this study, we aimed to investigate the function of Rho GTPase-activating protein 30 (ARHGAP30) in pancreatic cancer cells and thus propose a novel therapy for pancreatic cancer.

Methods

ARHGAP30 expression in tumor tissues from patients with pancreatic cancer as well as cell lines was detected using immunohistochemistry (IHC), real-time polymerase chain reaction, and western blotting. Cell proliferation, transwell, and apoptosis assays were performed and the levels of related proteins were determined after ARHGAP30 knockdown or overexpression. Additionally, in vivo experiments were performed on nude mice.

Results

ARHGAP30 expression was found to be significantly increased in tumor tissues from patients with pancreatic cancer as well as in pancreatic cancer cell lines. IHC and prognostic analyses indicated that patients with high ARHGAP30 expression had a good prognosis. ARHGAP30 overexpression significantly decreased pancreatic cancer cell proliferation and metastasis; promoted apoptosis; reduced β-catenin, B-cell lymphoma 2 (Bcl-2), matrix metalloproteinase-2 (MMP2), and MMP9 expression; and increased Bcl-2-associated X protein (Bax) and cleaved caspase-3 expression. ARHGAP30 knockdown elicited the opposite effects. The effects of ARHGAP30 knockdown were potently attenuated by the β-catenin inhibitor XAV939. ARHGAP30 knockdown-induced RHOA activity was potently attenuated by the RHOA inhibitor CCG1423. In vivo, ARHGAP30 overexpression significantly inhibited lung metastasis in nude mice and increased the survival of mice with lung metastases.

Conclusions

Our findings indicate that ARHGAP30 may function as a tumor suppressor in pancreatic cancer progression by regulating the expression of related genes and the β-catenin pathway.
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Metadata
Title
Upregulation of ARHGAP30 attenuates pancreatic cancer progression by inactivating the β-catenin pathway
Authors
Yongping Zhou
Zhiyuan Hua
Ye Zhu
Liying Wang
Fangming Chen
Ting Shan
Yunhai Zhou
Tu Dai
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01288-7

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