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.
Highlights
Colorectal cancer (CRC) is the second most frequent malignant cause of cancer-associated mortality worldwide, leading to ∼0.8 million new deaths per year (Bray et al, 2018)
The results revealed that β-arrestin1 was closely associated with the genes of epithelial-tomesenchymal transition (EMT), including Twist, Snail, CDH1, Vimentin, MMP2 and MMP9, and GSK-3β, NF-κB, phosphatidylinositol 3-kinase (PI3K)/Akts, mitogen-activated protein kinase (MAPK) signaling pathways were involved in regulating this process (Figure 1E)
Epithelial-to-mesenchymal transition is a crucial step for tumor cells to obtain invasive ability, which is essential in promoting tumor invasion and metastasis (Banyard and Bielenberg, 2015)
Summary
Colorectal cancer (CRC) is the second most frequent malignant cause of cancer-associated mortality worldwide, leading to ∼0.8 million new deaths per year (Bray et al, 2018). Multiple signaling pathways and key factors are involved in the migratory process of CRC cells from the primary sites into the distal locations/organs (Song et al, 2018). A series of results have shown that the epithelial-tomesenchymal transition (EMT) acts a vital role in promoting tumor invasion and metastasis (Samy et al, 2014). (Xia et al, 2018) Multiple signaling pathways, such as transforming growth factor-β (TGF-β)/SMAD, phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK), have been reported to regulate the EMT process (Derynck and Zhang, 2003; Mu et al, 2012; Zhang et al, 2018). The detailed mechanism in CRC remains unclarified (Nawshad et al, 2007; Sara et al, 2011; Duan et al, 2016; Liu et al, 2017)
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