β-Arrestin1 Promotes Colorectal Cancer Metastasis Through GSK-3β/β-Catenin Signaling- Mediated Epithelial-to-Mesenchymal Transition

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 tumo...

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Main Authors: Qing Song, Zhifen Han, Xinnan Wu, Yan Wang, Lihong Zhou, Liu Yang, Ningning Liu, Hua Sui, Jianfeng Cai, Qing Ji, Qi Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-04-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2021.650067/full
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author Qing Song
Qing Song
Qing Song
Zhifen Han
Zhifen Han
Xinnan Wu
Xinnan Wu
Yan Wang
Yan Wang
Lihong Zhou
Lihong Zhou
Liu Yang
Liu Yang
Ningning Liu
Ningning Liu
Hua Sui
Hua Sui
Jianfeng Cai
Qing Ji
Qing Ji
Qi Li
Qi Li
author_facet Qing Song
Qing Song
Qing Song
Zhifen Han
Zhifen Han
Xinnan Wu
Xinnan Wu
Yan Wang
Yan Wang
Lihong Zhou
Lihong Zhou
Liu Yang
Liu Yang
Ningning Liu
Ningning Liu
Hua Sui
Hua Sui
Jianfeng Cai
Qing Ji
Qing Ji
Qi Li
Qi Li
author_sort Qing Song
collection DOAJ
description 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.
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spelling doaj.art-dbf98965b54844bb8a408f8a0c03c79e2022-12-21T23:23:24ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-04-01910.3389/fcell.2021.650067650067β-Arrestin1 Promotes Colorectal Cancer Metastasis Through GSK-3β/β-Catenin Signaling- Mediated Epithelial-to-Mesenchymal TransitionQing Song0Qing Song1Qing Song2Zhifen Han3Zhifen Han4Xinnan Wu5Xinnan Wu6Yan Wang7Yan Wang8Lihong Zhou9Lihong Zhou10Liu Yang11Liu Yang12Ningning Liu13Ningning Liu14Hua Sui15Hua Sui16Jianfeng Cai17Qing Ji18Qing Ji19Qi Li20Qi Li21Department of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Chemistry, University of South Florida, Tampa, FL, United StatesDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaRecurrence 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.650067/fullcolorectal cancerepithelial-to-mesenchymal transitionmetastasisβ-arrestin1Wnt/β-catenin signaling pathway
spellingShingle Qing Song
Qing Song
Qing Song
Zhifen Han
Zhifen Han
Xinnan Wu
Xinnan Wu
Yan Wang
Yan Wang
Lihong Zhou
Lihong Zhou
Liu Yang
Liu Yang
Ningning Liu
Ningning Liu
Hua Sui
Hua Sui
Jianfeng Cai
Qing Ji
Qing Ji
Qi Li
Qi Li
β-Arrestin1 Promotes Colorectal Cancer Metastasis Through GSK-3β/β-Catenin Signaling- Mediated Epithelial-to-Mesenchymal Transition
Frontiers in Cell and Developmental Biology
colorectal cancer
epithelial-to-mesenchymal transition
metastasis
β-arrestin1
Wnt/β-catenin signaling pathway
title β-Arrestin1 Promotes Colorectal Cancer Metastasis Through GSK-3β/β-Catenin Signaling- Mediated Epithelial-to-Mesenchymal Transition
title_full β-Arrestin1 Promotes Colorectal Cancer Metastasis Through GSK-3β/β-Catenin Signaling- Mediated Epithelial-to-Mesenchymal Transition
title_fullStr β-Arrestin1 Promotes Colorectal Cancer Metastasis Through GSK-3β/β-Catenin Signaling- Mediated Epithelial-to-Mesenchymal Transition
title_full_unstemmed β-Arrestin1 Promotes Colorectal Cancer Metastasis Through GSK-3β/β-Catenin Signaling- Mediated Epithelial-to-Mesenchymal Transition
title_short β-Arrestin1 Promotes Colorectal Cancer Metastasis Through GSK-3β/β-Catenin Signaling- Mediated Epithelial-to-Mesenchymal Transition
title_sort β arrestin1 promotes colorectal cancer metastasis through gsk 3β β catenin signaling mediated epithelial to mesenchymal transition
topic colorectal cancer
epithelial-to-mesenchymal transition
metastasis
β-arrestin1
Wnt/β-catenin signaling pathway
url https://www.frontiersin.org/articles/10.3389/fcell.2021.650067/full
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