Filamin A regulates EGFR/ERK/Akt signaling and affects colorectal cancer cell growth and migration

The metastasis and recurrence rate, and the overall prognosis of colorectal cancer (CRC) remain unsatisfactory. Filamin A (FLNa), as an actin-binding protein, can interact with various signaling molecules and membrane receptors to affect cell signal transduction and function. However, whether FLNa is involved in the progression of CRC remains to be elucidated. The aim of the present study was to explore the role of FLNa in CRC cell proliferation and migration, as well as in the regulation of epidermal growth factor receptor (EGFR) signaling. Following transfection with a FLNa-targeting short hairpin RNA plasmid to knockdown expression of FLNa in the EGF-treated SW480 cell line, it was found that decreased expression of FLNa promoted cell proliferation and migration. Additionally, there was a negative correlation between FLNa levels and the activation of EGFR and Akt signaling pathways. Similarly, the expression of FLNa was significantly lower in human CRC tissues compared with adjacent normal tissues and FLNa expression was negatively correlated with the expression of Ki-67 in human CRC tissues. Although there was no significant difference in the Kaplan-Meier estimate of CRC between high expression and low expression of FLNa, there were significant negative associations between FLNa expression and TNM stage. The results suggested that FLNa may participate in EGF-induced cell proliferation and migration in CRC cells. Hence, interventions in the FLNa-mediated signaling pathway could provide attractive therapeutic targets for CRC.