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

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

doi:10.3389/fcell.2021.650067

Frontiers in Cell and Developmental Biology (Apr 2021)

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

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

Affiliations

Qing Song: Department of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Qing Song: Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Qing Song: Department of Medical Oncology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China
Zhifen Han: Department of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Zhifen Han: Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Xinnan Wu: Department of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Xinnan Wu: Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Yan Wang: Department of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Yan Wang: Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Lihong Zhou: Department of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Lihong Zhou: Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Liu Yang: Department of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Liu Yang: Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Ningning Liu: Department of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Ningning Liu: Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Hua Sui: Department of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Hua Sui: Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Jianfeng Cai: Department of Chemistry, University of South Florida, Tampa, FL, United States
Qing Ji: Department of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Qing Ji: Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Qi Li: Department of Medical Oncology and Cancer Institute of Integrative Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Qi Li: Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China

DOI: https://doi.org/10.3389/fcell.2021.650067
Journal volume & issue: Vol. 9

Abstract

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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.

Published in Frontiers in Cell and Developmental Biology

ISSN: 2296-634X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.frontiersin.org/journals/cell-and-developmental-biology

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