Hao Hu1,2,3,4,5, Shuo Zhang1,2, Shuming Xiong1,2, Benshun Hu1,5, Youzhao He1,5, Yuanlong Gu1,2,5. 1. Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China. 2. School of Medicine, Jiangnan University, Wuxi, China. 3. Department of Hepatobiliary and Pancreatic Surgery, The Third Hospital Affiliated to Nantong University, Wuxi, China. 4. School of Medicine, Nantong University, Nantong, China. 5. Wuxi Institute of Hepatobiliary Surgery, Wuxi, China.
Abstract
BACKGROUND: Recurrence and metastasis are the major causes of pancreatic ductal adenocarcinoma (PDAC) mortality after treatment. The underlying molecular mechanism is poorly understood. Actin-related protein 3 (ACTR3) is an important component of the actin-related protein 2/3 complex, which is involved in the regulation of cell motility and epithelial mesenchymal transition (EMT) process. Previously published studies have indicated that ACTR3 expression is upregulated in several types of cancers, and promotes tumor development, including gastric cancer and hepatocellular carcinoma. However, to date, the expression levels and the role of ACTR3 in PDAC are not well understood. METHODS: In the present study, the expression levels of ACTR3 in PDAC tissue and the relationship of ACTR3 expression with clinical prognosis were analyzed by mRNA microarray and bioinformatics. The biological functions and underlying mechanism of ACTR3 in PDAC were examined by a series of assays, including Cell Counting Kit-8 (CCK-8), transwell assay, and Western blotting. RESULTS: We found that the expression of ACTR3 was significantly increased in PDAC tissues and cell lines. A higher expression of ACTR3 was predictive of poor outcome for patients with PDAC. In vitro, the knockdown of ACTR3 expression significantly inhibited the invasive and migratory capacity of PDAC cells, and altered the distribution of F-actin and the expression of EMT markers. CONCLUSIONS: The findings of our study indicated that ACTR3 promotes cell migration and invasion by inducing EMT in PDAC, which may be a potential therapeutic target and prognostic indicator for PDAC patients. 2021 Journal of Gastrointestinal Oncology. All rights reserved.
BACKGROUND: Recurrence and metastasis are the major causes of pancreatic ductal adenocarcinoma (PDAC) mortality after treatment. The underlying molecular mechanism is poorly understood. Actin-related protein 3 (ACTR3) is an important component of the actin-related protein 2/3 complex, which is involved in the regulation of cell motility and epithelial mesenchymal transition (EMT) process. Previously published studies have indicated that ACTR3 expression is upregulated in several types of cancers, and promotes tumor development, including gastric cancer and hepatocellular carcinoma. However, to date, the expression levels and the role of ACTR3 in PDAC are not well understood. METHODS: In the present study, the expression levels of ACTR3 in PDAC tissue and the relationship of ACTR3 expression with clinical prognosis were analyzed by mRNA microarray and bioinformatics. The biological functions and underlying mechanism of ACTR3 in PDAC were examined by a series of assays, including Cell Counting Kit-8 (CCK-8), transwell assay, and Western blotting. RESULTS: We found that the expression of ACTR3 was significantly increased in PDAC tissues and cell lines. A higher expression of ACTR3 was predictive of poor outcome for patients with PDAC. In vitro, the knockdown of ACTR3 expression significantly inhibited the invasive and migratory capacity of PDAC cells, and altered the distribution of F-actin and the expression of EMT markers. CONCLUSIONS: The findings of our study indicated that ACTR3 promotes cell migration and invasion by inducing EMT in PDAC, which may be a potential therapeutic target and prognostic indicator for PDAC patients. 2021 Journal of Gastrointestinal Oncology. All rights reserved.
Authors: A Cano; M A Pérez-Moreno; I Rodrigo; A Locascio; M J Blanco; M G del Barrio; F Portillo; M A Nieto Journal: Nat Cell Biol Date: 2000-02 Impact factor: 28.824
Authors: J W Gilbert; B Wolpin; T Clancy; J Wang; H Mamon; A B Shinagare; J Jagannathan; M Rosenthal Journal: Ann Oncol Date: 2017-09-01 Impact factor: 32.976