Abstract
(1) Background: Epithelial-mesenchymal transition (EMT) is an essential step for cancer metastasis; targeting EMT is an important path for cancer treatment and drug development. NF-κB, an important transcription factor, has been shown to be responsible for cancer metastasis by enhancing the EMT process. Our previous studies showed that (20S)Ginsenoside Rh2 (G-Rh2) inhibits NF-κB activity by targeting Anxa2, but it is still not known whether this targeted inhibition of NF-κB can inhibit the EMT process. (2) Methods: In vivo (20S)G-Rh2-Anxa2 interaction was assessed by cellular thermal shift assay. Protein interaction was determined by immuno-precipitation analysis. NF-κB activity was determined by dual luciferase reporter assay. Gene expression was determined by RT-PCR and immuno-blot. EMT was evaluated by wound healing and Transwell assay and EMT regulating gene expression. (3) Results: Anxa2 interacted with the NF-κB p50 subunit, promoted NF-κB activation, then accelerated mesenchymal-like gene expression and enhanced cell motility; all these cellular processes were inhibited by (20S)G-Rh2. In contrast, these (20S)G-Rh2 effect were completely eliminated by overexpression of Anxa2-K301A, an (20S)G-Rh2-binding-deficient mutant of Anxa2. (4) Conclusion: (20S)G-Rh2 inhibited NF-κB activation and related EMT by targeting Anxa2 in MDA-MB-231 cells.
Highlights
Playing key roles in embryonic development, epithelial-mesenchymal transition (EMT) facilitates body formation and tissue differentiation [1,2,3,4]
Anxa2 Bound to NF-κB p50 Subunit in MDA-MB-231 Cells and MCF-7 Cells
It has been well-established that Anxa2 binds to p50 to promote NF-κB activation and cell survival in hepatocellular carcinoma and pancreatic cancer cell lines [28,29]
Summary
Playing key roles in embryonic development, epithelial-mesenchymal transition (EMT) facilitates body formation and tissue differentiation [1,2,3,4]. EMT is triggered by a genetic phenotype shift from epithelial-like to mesenchymal-like in response to pleiotropic signal; cells acquire the migratory and invasive properties by modifying adhesion molecules [3,4,5]. During this process, EMT specific transcription factors (EMT-TFs), in company with other regulatory factors like histone modifier and non-coding RNA, modify the gene expression through different states along EMT [6,7,8,9,10,11]. As its well-described clinical signature of EMT in cancer development, therapeutic strategies and targeted drugs towards EMT have been involved in cancer treatment [16,17,18]
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