To further assess the function of human ACTN4, we studied a lung carcinoma cell line expressing a mutated alpha-actinin-4, which is recognized as a tumor antigen by autologous CD8(+) cytotoxic T lymphocytes (CTL).
We newly established a monoclonal antibody specifically recognizing the product of the alternatively spliced ACTN4 transcript (namely, variant actinin-4), and used it to examine the expression of variant actinin-4 immunohistochemically in a total of 609 surgical specimens of various histological subtypes of lung cancer.
A quantitative immunohistochemical assessment of lung cancer tissues revealed that ACTN4 protein level was considerably higher in cancerous tissues than in the adjacent normal ones, and the area under the receiver operating characteristic curve was 0.736 (p < 0.001).
In the tumor cells, a point mutation generates an amino-acid change that is essential for recognition by the CTLS: The mutation was not found in alpha-actinin-4 cDNA sequences from about 50 lung carcinoma cell lines, suggesting that it is unique to this patient.
Furthermore, the bioinformatics analysis of gene expression in lung cancer patients suggested that overexpression of ACTN4 correlated with poor survival prognosis.
The contribution of ACTN4 to the process of lung cancer metastasis to the brain could be mainly through regulation of actin cytoskeleton reorganization, cell motility, and focal adhesion.