CD24 regulates cell proliferation and transforming growth factor β‐induced epithelial to mesenchymal transition through modulation of integrin β1 stability

• Published in: Cellular signalling 2012-11, Vol.24 (11), p.2132-2142
• Main Authors: Lee, Kyung-min, Ju, Ji-hyun, Jang, Kibeom, Yang, Wonseok, Yi, Jae Youn, Noh, Dong Young, Shin, Incheol
• Format: Article
• Language: English
• Subjects: CD24; CD24 Antigen - chemistry; CD24 Antigen - genetics; CD24 Antigen - metabolism; Cell Proliferation - drug effects; Down-Regulation - drug effects; EMT; Epithelial-Mesenchymal Transition - drug effects; ERK; Extracellular Signal-Regulated MAP Kinases - metabolism; FAK; Focal Adhesion Kinase 1 - metabolism; G1 Phase Cell Cycle Checkpoints - drug effects; HEK293 Cells; Humans; Integrin; Integrin beta1 - metabolism; MCF-7 Cells; Mitogen-Activated Protein Kinase Kinases - metabolism; Phosphorylation; Protein Binding; Protein Stability; raf Kinases - metabolism; RNA Interference; RNA, Small Interfering - metabolism; Signal Transduction - drug effects; Transforming Growth Factor beta1 - pharmacology
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2012.07.005

To determine the role of CD24 in breast cancer cells, we knocked down CD24 in MCF-7 human breast cancer cells by retroviral delivery of shRNA. MCF-7 cells with knocked down CD24 (MCF-7 hCD24 shRNA) exhibited decreased cell proliferation and cell adhesion as compared to control MCF-7 mCD24 shRNA cells. Decreased proliferation of MCF-7 hCD24 shRNA cells resulted from the inhibition of cell cycle progression from G1 to S phase. The specific inhibition of MEK/ERK signaling by CD24 ablation might be responsible for the inhibition of cell proliferation. Phosphorylation of Src/FAK and TGF-β1-mediated epithelial to mesenchymal transition was also down-regulated in MCF-7 hCD24 shRNA cells. Reduced Src/FAK activity was caused by a decrease in integrin β1 bound with CD24 and subsequent destabilization of integrin β1. Our results suggest that down-regulation of Raf/MEK/ERK signaling via Src/FAK may be dependent on integrin β1 function and that this mechanism is largely responsible for the CD24 ablation-induced decreases in cell proliferation and epithelial to mesenchymal transition. ► Knock-down of CD24 decreased proliferation of MCF-7 cells ► Phosphorylation of Src/FAK and TGF-β1-mediated epithelial to mesenchymal transition were down-regulated by CD24 ablation ► A decrease in integrin β1 bound with CD24 and subsequent destabilization of integrin β1 resulted in reduced Src/FAK activity