Biological significance of actinin-4 in the mechanism of cancer invasion and metastasis

  • Honda Kazufumi
    Division of Chemotherapy and Clinical Research National Cancer Center Research Institute
  • Umaki Tomoko
    Division of Chemotherapy and Clinical Research National Cancer Center Research Institute
  • Miura Nami
    Division of Chemotherapy and Clinical Research National Cancer Center Research Institute
  • Miyanaga Akihiko
    Division of Chemotherapy and Clinical Research National Cancer Center Research Institute
  • Masuda Mari
    Division of Chemotherapy and Clinical Research National Cancer Center Research Institute
  • Watanabe Takafumi
    Division of Chemotherapy and Clinical Research National Cancer Center Research Institute
  • Watabe Yukio
    Division of Chemotherapy and Clinical Research National Cancer Center Research Institute
  • Yamada Tesshi
    Division of Chemotherapy and Clinical Research National Cancer Center Research Institute

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Other Title
  • がん浸潤・転移機構におけるアクチニン-4の生物学的意義

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Abstract

In cancer clinical practice, metastasis is an important prognostic factor, and so elucidation of the mechanism of metastasis at the molecular level is desirable. Cell motility is intricately related to metastasis, and dynamic change in the actin cytoskeleton is one of the most important factors regulating motility. Actinin-4 (gene name: ACTN4), which is a novel actin bundling protein, has been identified by our laboratory. Expression of actinin-4 protein leads to the formation of cell processes and increases motility. Clinicopathologically, increased expression of actinin-4 protein not only affects the prognosis in invasive ductal carcinoma of the breast, but also correlates with lymph node metastasis in colon cancer. In small cell lung cancer, a splice variant has been isolated as a cancer/testis antigen, and may also serve as a diagnostic marker. Recently, increases in actinin-4 protein were found to be attributable to ACTN4 gene copy number amplification. ACTN4 gene amplification has been identified in ovarian and pancreatic cancer. This review discusses the biological role of actinin-4 in cancer metastasis and invasion.

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