Abstract
Invasion and metastasis are malignant phenotypes in cancer that lead to patient death. Cell motility is involved in these processes. In 1998, we identified overexpression of the actin-bundling protein actinin-4 in several types of cancer. Protein expression of actinin-4 is closely associated with the invasive phenotypes of cancers. Actinin-4 is predominantly expressed in the cellular protrusions that stimulate the invasive phenotype in cancer cells and is essential for formation of cellular protrusions such as filopodia and lamellipodia. ACTN4 (gene name encoding actinin-4 protein) is located on human chromosome 19q. ACTN4 amplification is frequently observed in patients with carcinomas of the pancreas, ovary, lung, and salivary gland, and patients with ACTN4 amplifications have worse outcomes than patients without amplification. In addition, nuclear distribution of actinin-4 is frequently observed in small cell lung, breast, and ovarian cancer. Actinin-4, when expressed in cancer cell nuclei, functions as a transcriptional co-activator. In this review, we summarize recent developments regarding the biological roles of actinin-4 in cancer invasion.
Highlights
Despite successful complete resection at the primary cancer site, poor outcomes are occasionally observed in patients due to failure to control distant metastasis
Isolation of ACTN4, a metastasis‐related gene We generated a mouse monoclonal antibody that strongly reacts to the highly invasive phenotype of breast carcinoma, and we identified the full-length cDNA for the protein that was recognized by this antibody
If patients with stage I adenocarcinoma of the lung with potential metastasis can be identified with ACTN4 amplification of surgical specimens, adjuvant chemotherapy for such patients may have a clinical benefit in terms of patient selection
Summary
Despite successful complete resection at the primary cancer site, poor outcomes are occasionally observed in patients due to failure to control distant metastasis. Overexpression of actinin-4 and EMT are observed in cells at the invasive front. An siRNA-mediated decreased in actinin-4 protein in a colon cancer cell line (SW480) reduces the cellular protrusions that are associated with cancer invasion [23].
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