RNAi-mediated downregulation of alpha-actinin-4 decreases invasion potential in oral squamous cell carcinoma

alpha-actinin-4, originally identified as ail actin-binding protein associated with cell motility, invasion, and metastasis of cancer cells, appears to be overexpressed in various human epithelial carcinomas, including colorectal, breast, esophageal, ovarian, and non-small cell lung carcinomas. The authors evaluated whether alpha-actinin-4 might be appropriate as a Molecular target for cancer gene therapy. In 64 primary oral squarnous cell carcinomas (OSCCs) and 10 normal oral mucosal specimens, and in Seven human OSCC cell lines, alpha-actinin-4 expression was evaluated immunologically and correlations with clinicopathologic factors were examined. Overexpression of alpha-actinin-4 was detected in 38 of 64 oral squamous cell carcinomas (70%); significantly more Frequently than in normal oral mucosa. The expression of a-actinin-4 was significantly associated with invasion potential defined by the Matrigel invasion assay. Cancer cell lines with higher alpha-actinin-4 expression had greater invasive potential. An RNAi-mediated decrease in alpha-actinin-4 expression reduced the invasion potential. These results indicated that the overexpression of alpha-actinin-4 was associated with an aggressive phenotype of OSCC. The Study indicated that alpha-actinin-4 Could be a potential molecular target for gene therapy by RNAi targeting for OSCC.