Carcinogenesis Research Group
Division of Cancer Differentiation

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Research Staff

Research Activities

In many patients that suffer from solid cancers, the presence or absence of unresectable metastases profoundly affects their prognosis. Understanding mechanisms by which cancer cells with metastatic ability emerge during carcinogenesis and eventually form metastatic foci in distant organs is crucial in eradicating metastasis.

In order to understand the mechanisms of cancer metastasis, we analyzed metastasis of human colon cancer and other solid tumors using immunocompromised mice. Through functional screening of shRNA or microRNA library (Izumiya et al., 2010, Izumiya et al., 2010), novel regulators of liver metastasis of colon cancer have been isolated (Okamoto et al., 2012). We will analyze functions of these regulators, and use them as starting points to elucidate mechanisms of metastasis.

As a second approach to understanding metastatic processes, we started biological and biochemical characterization of cancer stem cells. It has been pointed out by many researchers that metastatic cancer cells and cancer stem cells are similar in terms of their biological behaviors as well as gene expression profiles. Thus, cancer stem cells may play pivotal roles not only in carcinogenesis but also in efficient formation of metastatic foci. In addition, cancer stem cells are likely to be implicated in other unfavorable behaviors of cancer cells, such as resistance to chemotherapy. In the context of possible crucial roles of cancer stem cells in metastasis and other deadly traits, we isolated human colon cancer stem cells and maintained them in an in vitro spheroid cultivation system. We will biochemically characterize these cells in order to understand mechanisms by which cancer stem cells develop life-threatening abilities. Regulation of stem cell-related genes (Ishiguro et al., 2011) as well as oncogenic and tumor suppressor pathways, such as the p53 pathway (Okamoto et al., 2002, Shinozaki et al., 2003, Okamoto et al., 2005, Okamoto et al, 2009), will also be explored.