Oncology reports
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The metastatic properties of cancer cells result from genetic and epigenetic alterations that lead to the abnormal expression of key genes regulating tumor phenotypes. Recent discoveries suggest that aberrant DNA methylation provides cancer cells with advanced metastatic properties; however, the precise regulatory mechanisms controlling metastasis-associated genes and their roles in metastatic transformation are largely unknown. We injected SK-OV-3 human ovarian cancer cells into the perineum of nude mice to generate a mouse model that mimics human ovarian cancer metastasis. ⋯ Next, we explored the functional role of AGR2 in the metastatic transformation of SK-OV-3 cells. SK-OV-3 cells overexpressing AGR2 showed increased migratory and invasive activity. Our results indicate that DNA methylation within the AGR2 promoter modulates more aggressive cancer cell phenotypes.
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In the present study, we evaluated the role of phosphatidylinositol-3 OH kinase/protein kinase B (PI3K/Akt) signaling on changes to epithelial-to-mesenchymal reverting transition (EMrT) in nasopharyngeal carcinoma (NPC). Protein expression levels of p-Akt (Ser473), and the epithelial‑to-mesenchymal transition (EMT) markers E-cadherin, vimentin, α smooth muscle actin (α-SMA), were examined in clinical samples from 130 cases of undifferentiated non-keratinizing NPC, and 20 cases of benign nasopharyngitis. The relationship between protein expression levels and the statue of NPC lymph node metastasis was analyzed. ⋯ Treating CNE2Z cells with LY294002 inhibited p-Akt (Ser473), vimentin and α-SMA expression but upregulated E-cadherin expression, leading to significantly attenuated cell invasion and migration. Administration of mice with LY294002 resulted in upregulation of membrane E-cadherin, and downregulation of vimentin and α-SMA in CNE2Z xenografts, with reduced pulmonary metastasis. Our findings suggest that inhibiting the PI3K/Akt pathway using LY294002 attenuated NPC metastasis via induction of EMrT.