Oct4 在肺癌中調控 osteopontin 的角色與機制探討

Abstract

Octamer 4 (also known as Oct4 and Pou5f1) and osteopontin (OPN) are two prognostic factors for survival in lung cancer patients. Oct4, a member of the POU transcription factors, is regarded as a multifunctional factor and plays an oncogenic role through maintaining characteristics of cancer stem cells. Our previous results demonstrated that downregulation of Oct4 expression reduced bladder cancer cell migration and invasive ability. Therefore, we proposed that Oct4 might correlate with cancer cell metastasis. OPN is an O-glycosylated phosphoprotein and regulates cancer cell migration and invasion through binding to αvβ integrin and CD44 variant receptors. Previous microarray data revealed that knockdown of Oct4 in embryonic stem cell decreased OPN expression. In this study, we investigated whether modulation of OPN expression by Oct4 correlated with the migration and invasion of lung cancer cells. High levels of Oct4 and OPN expression were detected in the clinical samples of late-stage human lung tumors. Furthermore, mRNA and protein levels of OPN were also increased in Oct4-overexpressing A549 cells. Knockdown of OPN expression in Oct4-overexpressing lung cancer cells promoted migratory ability in the Boyden chamber assay. These results suggest that the promotion of tumor metastasis by Oct4 may be mediated through the enhancement of the OPN promoter activity. We will further study whether Oct4-mediated OPN expression is associated with epithelial-mesenchymal transition (EMT) and migration and invasion of lung cancer cells in vitro and in animal models.