β-Arrestin1 Promotes Colorectal Cancer Metastasis Through GSK-3β/β-Catenin Signaling- Mediated Epithelial-to-Mesenchymal Transition
Authors: Zhifen Han
Qing Ji
Xinnan Wu
Ningning Liu
Lihong Zhou
Yan Wang
Qing Song
Qi Li
Liu Yang
Hua Sui
Jianfeng Cai
Journal: Frontiers in Cell and Developmental Biology (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Wnt/β-catenin signaling pathway; colorectal cancer; epithelial-to-mesenchymal transition; metastasis; β-arrestin1.
Affiliations: Department of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China., Department of Chemistry, University of South Florida, Tampa, FL, United States.

Abstract:  Recurrence and metastasis seriously affects the prognosis of patients with tumors, and the epithelial-to-mesenchymal transition (EMT) plays a key role in promoting tumor invasion and metastasis. Previous studies have showed that β-arrestin1 acted as a tumor-promoting factor in multiple types of tumor. However, the exact role and mechanism of β-arrestin1 in colorectal cancer (CRC) progression remains to be elucidated. Our research aimed to explore the potential mechanism underlying the role of β-arrestin1 in CRC metastasis. The expression of β-arrestin1 was investigated in both primary and metastatic CRC tissues using the GSE41258 database, and it was revealed that CRC patients with liver/lung metastasis had a higher expression level of β-arrestin1, and the expression level of β-arrestin1 was inversely correlated with the prognosis of CRC patients. Further in vitro mechanism studies indicated that β-arrestin1 had the ability to promote the migration of CRC cells through regulating the EMT process by activating Wingless/integration-1 (Wnt)/β-catenin signaling pathways. Blocking Wnt/β-catenin signaling with inhibitor ICG001 decreased the promoting effect of β-arrestin1 on EMT in CRC. In vivo imaging experiments further demonstrated the promoting effect of β-arrestin1 on the lung metastasis of CRC cells by tail vein injection in mice. The results of this paper suggest that β-arrestin1 promotes EMT via Wnt/β-catenin signaling pathway in CRC metastasis, and provides a novel therapeutic target for CRC metastasis. 

Retracted: No

PubPeer comments:
 An image in Figure 7F seems to appear in Figure 5A of an earlier paper with overlapping authorship, where it seems to be described differently: Frontiers in Pharmacology (2020), doi: 10.3389 fphar.2020.586616, discussed here: https: pubpeer.com publications 5566C44920ABEAE356971B671EED1D#2. Could the authors please check? *** ![file] , 
 Dear Actinopolyspora biskrensis, We thank you for pointing out the important mistake in Figure 5A. We are very sorry for our mistake. Our experiments in referred two papers were performed at the same time, and therefore some data was deal with together, including the immunohistochemical results of Snail. In figure 5A (Frontiers in Pharmacology, 2020), by checking the original data, we find that we have misused one immunohistochemical picture of Snail (Tan IIA-M). We will provide the correct picture (Tan IIA-M) to replace the wrong one to make up for the mistake. However, in the Figure 7F of the paper in Frontiers in Cell and Developmental Biology (2021), the immunohistochemical pictures for Snail were right provided. To correct our mistake in Figure 5A (Frontiers in Pharmacology, 2020), we will ask for the editor office of Frontiers in Pharmacology to provide the right data. In the future work, we will try our best to avoid such mistakes. We thank again for your raising of this important issue. Your valuable comments are very welcome again. ![file] ,