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Home > Organization > Fundamental Innovative Oncology Core > Biomarker and Therapeutic Target Research Core > Department of Biomarkers for Early Detection of Cancer > Research Projects > Molecular mechanisms of cancer invasion and metastasis

Molecular mechanisms of cancer invasion and metastasis

Metastasis is one of the major obstacles in the treatment of any cancer. Surgical management of cancer with no lymph node or organ metastasis is generally uncomplicated, but the treatment of metastatic disease remains challenging. We focus on molecules involved in invasive and metastasis and analyze these molecular mechanisms. In addition, circulating tumor cells (CTC) are thought to have the metastatic ability to multiple organs; therefore, it is important to study CTC in order to understand metastasis.

Analysis of molecular mechanisms of actinin-4

Acquisition of increased motility by cancer cells seems to be a requirement for cancer invasion and metastasis, and during the process of cell movement, the actin cytoskeleton is dynamically remodeled by the functions of various classes of actin-binding proteins. In our department, Honda et al. isolated ACTN4 as an actin-binding protein involved in the bundling of actin fibers and promotion of cell motility. We are analyzing the medical and biological significance of ACTN 4 for cancer.

In pancreatic cancer, ovarian cancer, colon cancer, esophageal cancer, and head and neck cancer, the overall survival time of the ACTN4 high expression patient group was significantly shorter than that of the low expression patient group. In stage I lung adenocarcinoma, the patient group with ACTN4 gene amplification had a significantly higher risk of death when compared to the patient group without gene amplification. In addition, an ACTN4 splice variant that is expressed specifically in lung high-grade neuroendocrine tumor (LCNEC) was useful for diagnosis of LCNEC, and we found that the ACTN4 splice variant is a biomarker for predicting prognosis. Furthermore, we clarified that overexpression and knockdown of ACTN4 in cell lines is correlated with cell motility.

Analysis of the molecular mechanism of CTC

CTC are tumor cells that have passed into the blood from cancer tissue and are thought to have metastatic potential. There are thought to be few CTC in the blood, and it is difficult to analyze the molecular mechanisms of these cells. Therefore, we aim to analyze the functions of CTC using various omics analytical methods.