ABSTRACT
FYN, one of the members of the Src family of kinases (SFKs), has been reported to be overexpressed in various types of cancers and correlated with cell motility and proliferation. However, the mechanism is still unclear. In the present study, we found that FYN was overexpressed in breast cancer and overexpression of FYN promoted cell proliferation, migration and invasion in the MCF10A cells, whereas depletion of FYN suppressed cell proliferation, migration and invasion in the MDA-MB-231 cells. Moreover, FYN upregulated the expression of mesenchymal markers and epithelial-mesenchymal transition (EMT)-related transcription factors, and downregulated the expression of epithelial markers, suggesting that FYN induces EMT in breast cancer cells. Furthermore, FYN was transcriptionally regulated by FOXO1 and mediated FGF2-induced EMT through both the PI3K/AKT and ERK/MAPK pathways.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/pathology , Epithelial-Mesenchymal Transition/genetics , Proto-Oncogene Proteins c-fyn/genetics , Breast/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Disease Progression , Down-Regulation/genetics , Female , Fibroblast Growth Factor 2/genetics , Forkhead Box Protein O1/genetics , Humans , MCF-7 Cells , Mitogen-Activated Protein Kinase Kinases/genetics , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Signal Transduction/genetics , Transcription Factors/genetics , Up-Regulation/geneticsABSTRACT
MicroRNAs act as key regulators in carcinogenesis and progression in various cancers. In present study, we explored the role of miR-340 in the breast cancer progression. Our results showed that overexpression of miR-340 inhibits breast cancer cell proliferation and invasion, whereas depletion of miR-340 promotes breast cancer progression. Molecularly, ZEB1 was identified as a target gene of miR-340 and miR-340 suppressed the expression of ZEB1 by directly binding to the 3'-UTR of ZEB1. Furthermore, ZEB1 transcriptionally suppresses miR-340 expression. The negative feedback loop regulated TGF-ß-mediated breast cancer progression. In conclusion, our data suggested that miR-340 acted as a tumor suppressor in breast cancer progression.
