The tetraspanin CD9 has previously been shown to be involved in various cellular activities, including proliferation and migration. In addition, CD9 has been shown to be associated with epidermal growth factor receptor (EGFR). A common characteristic of glioblastoma multiforme histology is EGFR amplification, which affects signal transduction processes. The anti-proliferative effects of CD9 have been linked to EGFR signaling pathways, including phosphorylation of phosphoinositide-3-kinase (PI3K)/Akt and activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (Erk). The present study demonstrated that CD9 decreased the phosphorylation of EGFR at specific sites. In addition, CD9 attenuated EGFR signaling of PI3K/Akt and MAPK/Erk, which was associated with cell growth and proliferation. Conversely, small hairpin RNA-mediated knockdown of CD9 expression enhanced the activation of EGFR signal transduction pathways, including PI3K/Akt and MAPK/Erk. These results suggested that the mechanism underlying CD9-induced suppression of cell proliferation may involve the inhibition of phosphorylation of EGFR and the activity of PI3K/Akt and MAPK/Erk signaling pathways.
