Abstract
BackgroundLiver metastasis is the most common cause of death in patients with colorectal cancer (CRC). Phosphatase of regenerating liver-3 induces CRC metastasis by epithelial-to-mesenchymal transition, which promotes CRC cell liver metastasis. Mesenchymal-to-epithelial transition (MET), the opposite of epithelial-to-mesenchymal transition, has been proposed as a mechanism for the establishment of metastatic neoplasms. However, the molecular mechanism of MET remains unclear.MethodsUsing Immunohistochemistry, western blotting, invasion assays, real-time quantitative PCR, chromatin immunoprecipitation, luciferase reporter assays, human miRNA arrays, and xenograft mouse model, we determined the role of hepatocyte exosome-derived miR-203a-3p in CRC MET.ResultsIn our study, we found that miR-203a-3p derived from hepatocyte exosomes increased colorectal cancer cells E-cadherin expression, inhibited Src expression, and reduced activity. In this way miR-203a-3p induced the decreased invasion rate of CRC cells.CoclusionMiR-203a-3p derived from hepatocyte exosomes plays an important role of CRC cells to colonize in liver.
Highlights
Liver metastasis is the main cause of death in patients with colorectal cancer (CRC)
MRNA expression confirmed same E-cad/ Vimentin expression in different CRC stage samples and liver metastasis specimens (Fig. 1B-F). These results suggest that CRC cells undergo a change from epithelial-to-mesenchymal transition (EMT) to mesenchymal-to-epithelial transition (MET) in the progression of liver metastases
Metastasis is the primary cause of death in patients with cancer, which is a multistep process including the detachment of cancer cells from the primary site and their transport into the blood vessels and colonization to distal organs; this process allows tumor cells to disseminate from their primary site and establish secondary tumors at secondary sites
Summary
Liver metastasis is the main cause of death in patients with colorectal cancer (CRC). Xu et al BMC Cancer (2021) 21:718 once cancer cells colonize to specific organs, the reexpression of E-cadherin can be observed in the metastasis sites, indicating that cancer cells undergo the phenotypic mesenchymal-to-epithelial transition (MET), which is regulated by the tumor microenvironment. Our previous study revealed that PRL-3 could activate the NF-κB pathway to induce KCNN4 expression, leading to the inhibition of E-cadherin expression and the promotion of CRC liver metastasis [14]. Various signaling pathways have been implicated in PRL-3induced EMT and it is well known that cancer cells need to undergo MET before colonizing the liver, whether PRL-3 regulates the progression of MET remains unknown. A recent study has revealed that PRL-3 could induce the activation of the epidermal growth factor receptor (EGF)/EGFR (epidermal growth factor receptor) signaling pathway; this finding indicates that PRL-3 may be involved in the progression of MET [15].
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