• Oncometabolite D-2-Hydroxyglurate Directly Induces Epithelial-Mesenchymal Transition and is Associated with Distant Metastasis in Colorectal Cancer (Scientific Reports, 2016)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Colvin et al. demonstrate that in colorectal cancer cells that even in the absence of isocitrate dehydrogenase (IDH) mutation, the levels of the oncometabolite D-2 hydroxyglutarate (D-2HG) and its enantiomer L-2HG were elevated through glutamine anaplerosis. D-2HG, but not L-2HG, increased the trimethylation of histone H3 lysine 4 of the promoter region of ZEB1 , the master regulator of epithelial-mesenchymal transition (EMT), also increased the expression of the ZEB1 gene to directly induce EMT in colorectal cancer cells. Furthermore, they demonstrated that D-2HG levels to be elevated in colorectal cancer specimens, particularly in those associated with distant metastasis, supporting the observations in vitro and implicating the contribution of D-2HG in metastasis, the major cause of death in this disease.

  • Cell-free culture conditioned medium elicits pancreatic β-cell lineage-specific epigenetic reprogramming (Oncology Reports, 2016)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Kawamoto and Ohashi et al. demonstrate that cell-free culture conditioned medium elicits pancreatic β-cell lineage-specific epigenetic reprogramming in mice. The study showed that the transfer of epigenetic phenotypes was achieved in the cell-free system of pancreatic insulinoma cell culture. These findings provide further support for the utility of cell-free conditioned medium for cellular reprogramming and the regenerative medicine.

  • The importance of one carbon (C1) metabolism: mitochondrial folate enzymes in human colorectal cancer ( Oncology Reports, 2016)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Miyo et al. demonstrate that the importance of mitochondrial folate enzymes of one carbon (C1) metabolism in human colorectal cancer. The data indicate that three mitochondrial folate metabolic enzymes, serine hydroxymethyl transferase (SHMT2), methylenetetrahydrofolate dehydrogenase (MTHFD2), and aldehyde dehydrogenase 1 family member L2 (ALDH1L2), play a role in human colorectal tumor tissues. The present study demonstrates that C1 metabolic enzymes could provide a potential therapeutic strategy for treating colorectal cancer.

  • Clinical significance of histone demethylase NO66 in invasive colorectal cancer (Annal. Surg. Oncology, 2016)
    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Nishizawa et al. demonstrate that the oncogene-regulated histone demethylase, nucleolar protein 66 (NO66), which is known to work coordinately with the well-characterized oncogene c-MYC, are critical for the determination of biological behavior of invasive colorectal cancer. This would facilitate new drug discovery for the intractable cancer.

  • c-Met affects gemcitabine resistance in mouse model of pancreatic cancer (Oncology Letters, 2016 )
    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Noguchi et al. studied a  mouse Kras/Met   model of pancreatic cancer stem cells (CSCs) and  showed that  c-Met inhibition in Kras mice significantly decreased pancreatic intraepithelial neoplasia (PanIN)  lesions, suggesting that complete c-Met signal inhibition with chemotherapy could be useful for control of pancreatic malignant features.

  • Fetal-hepatocyte-derived culture medium elicits adipocyte differentiation into bile-duct-cell lineage in mouse (Biomedical Reports, 2016 )

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Ogawa et al.  studied fetal tissues of mouse and showed that fetal-hepatocyte-derived factors elicit the differentiation to bile-duct-cell lineages, suggesting that fetal cells possess multiple potentials that are absent in adults.

  • Mathematical linkage analysis of transcriptome and metabolome in cancer stem cell (Scientific Reports, 2016)
    The bioinformatics and computational modeling are expected to offer innovative approaches in human medical science.  In collaboration with the Department of Surgery, Osaka University (Profs. Yuichiro Doki and Masaki Mori), as well as the  Faculty of Mathematics, Kyushu University  (As. Prof. Hidetoshi Matsui),  Koseki et al. reported  the computational analysis and prediction of transcriptome and metabolome datasets, which were identified from fluorescent-based visualized system of chemo-resistant cancer stem cells in human esophagus. The present study fastens the further rational to innovative drug discovery against robust cancer stem cells.

  • BRAF V600E inhibition stimulates AMPK-mediated autophagy in colorectal cancer  (Scientific Reports, 2016)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Sueda et al. demonstrate that selective BRAF V600E inhibition activates AMP-activated protein kinase (AMPK), which induces autophagy as a mechanism of therapeutic resistance in human cancers. Present experiments suggest that the control of autophagy contributes to overcome the chemoresistance of BRAF V600E  cancer cells.

  • A crucial EMT regulator, Sox4/Ezh2 axis is closely related to the clinical outcome in pancreatic cancer patients (Int J Oncol, 48, 2015)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Hasegawa et al. showed that Sox4/Ezh2 axis was closely associated with the prognosis in pancreatic cancer patients. Sox4 is indispensable for epithelial-mesenchymal transition (EMT) and regulates various kinds of master regulators. Sox4 induces the transcription of Ezh2, the histone methyltransferase, which was counteracted by miR-335. The expression study with laser captured microdissection (LCM) samples indicated a critical role of the Sox4/Ezh2 axis in the EMT control of pancreatic cancer.

  • Embryonic microRNA-369 controls metabolic splicing factors and urges cellular reprograming (PLOS ONE, 2015)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Konno et al. found a unique role of the embryonic miR-369- HNRNPA2B1  axis in controlling metabolic enzyme function. The data suggest a novel pathway linking epigenetic, transcriptional, and metabolic control in cell reprogramming, and may be useful for the novel diagnostic approaches and therapies in regenerative medicine and cancer research.