Cancer Institute

  • Kounosuke Watabe

    kounosuke_watabe.jpgDeputy Director for Basic Science
    Professor, Department of Microbiology and Biochemistry
    Cancer Genetics Program
    PhD, Biochemistry, 1981, Kyoto University, Japan
    Postdoc, 1981-85, University of Arizona Health Science Center

    Contact information
    2500 N State St., Suite G651-07
    Jackson, MS 39216
    Phone: (601) 815-8305
    Fax: (601) 815-6806

    Research interests

    • Tumor metastasis of breast and prostate cancers
    • Cancer stem-like cells and tumor dormancy
    • Tumor microenvironment

    Research synopsis

    The studies of our laboratory focus on the molecular mechanism of tumor metastasis in breast and prostate cancers. Much of the lethality of malignant neoplasms is attributable directly to their ability to develop secondary growths in organs at a distance from the primary tumor mass. Our group has been working on tumor metastasis suppressor genes including KAI1 and NDRG1and trying to elucidate the roles of these genes in cancer stem-like cells (CSCs), in the context of tumor microenvironment. We are also working on tumor-stromal cells interaction by particularly focusing on Notch signaling, hyaluronic acid and BMP7 (bone morphogenetic protein 7) in bone and brain metastasis. We have recently found that BMP7 secreted from bone stromal cells induces senescence in CSCs by activating p38 MAPK and increasing expression of p21 and NDRG1, indicating that the BMP7-p38-NDRG1 axis plays a critical role in dormancy and recurrence of CSCs in bone and suggests a potential therapeutic utility of BMP7 for recurrent metastatic disease. Due to our discovery, BMP7 was named as the 2011 Molecule of the Year by The International Society for Molecular and Cell Biology and Biotechnology Protocols and Research. The long term goal of this line of research is to construct a molecular map of metastasis cascade signaling, which can eventually lead to identification of better diagnostic markers and therapeutic targets for this devastating disease. Another major focus of our research is tumor metabolism, particularly in lipogenesis, at an early stage of breast cancer. We have recently identified multiple microRNAs and lincRNAs that play critical roles in CSCs of breast cancer and in-depth analysis of these molecules are currently underway.

    Selected publications

    • Fei Xing, Hiroshi Okuda, Aya Kobayashi, Misako Watabe, Sudha K. Pai, Puspa R. Pandey, Shigeru Hirota, Brian E. Moore, Wen Liu, Koji Fukuda, Vishnu Modur, Megumi Iiizumi1, Andrew Wilber, Elizabeth Peralta and Kounosuke Watabe. (2013) Reactive astrocytes promote the growth of cancer stem-like cells of metastatic breast tumor by activating Notch signaling in brain. EMBO Mol. Med. 5, 384 (cover story). PubMed link
    • Hiroshi Okuda*, Fei Xing* Puspa R Pandey, Sambad Sharma, Misako Watabe, Sudha K. Pai, Yin-Yuan Mo, Megumi Iiizumi- Gairani, Shigeru Hirota, and Kounosuke Watabe. (2013) miR-7 suppresses brain metastasis of cancer stem-like cells by modulating Kruppel-like factor 4 in breast cancer. Cancer Res, 73, 1434 (cover story) * equal contribution. PubMed link
    • Puspa R. Pandey, Fei Xing, Sambad Sharma, Misako Watabe, Sudha K. Pai, Megumi Iiizumi- Gairani, Koji Fukuda, Shigeru Hirota, Yin-Yuan Mo and Kounosuke Watabe (2012) Elevated lipogenesis in epithelial stem-like cell confers survival advantage in ductal carcinoma in situ of breast cancer. Oncogene, 10.519. PubMed link
    • Wen Liu*, Fei Xing*, Megumi Iiizumi-Gairani, Hiroshi Okuda, Misako Watabe, Sudha K. Pai, Puspa R. Pandey, Shigeru Hirota, , Aya Kobayashi, Yin-Yuan Mo, Koji Fukuda, Yi Li  and Kounosuke Watabe. (2012) Metastasis suppressor, NDRG1, pleiotropically inhibits tumor metastasis by modulating Wnt-β-catenin signaling: Targeting Wnt-NDRG1 pathway as a potential therapeutic opportunity. EMBO Mol. Med., 4, 93. * equal contribution. PubMed link  
    • Hiroshi Okuda, Aya Kobayashi, Bo Xia, Misako Watabe, Sudha K Pai, Shigeru Hirota, Fei Xing, Wen Liu, Puspa R Pandey, Koji Fukuda, Vishnu Modur, Arnab Ghosh, Andrew Wilber and Kounosuke Watabe. (2012) HAS2 promotes metastasis by stimulating interaction of breast cancer stem cells with macrophage and stromal cells in the bone. Cancer Research, 72, 537. PubMed link
    • Aya Kobayashi, Hiroshi Okuda, Puspa R. Pandey, Misako Watabe, Shigeru Hirota, Sudha K. Pai, Fei Xing, Wen Liu, Koji Fukuda, Christopher Chambers and Kounosuke Watabe . (2011) Roles of BMP7 in dormancy and recurrence of prostate cancer stem-like cell in bone. J. Exp. Med. 208, 2641. PubMed link
    • Wen Liu, Megumi Iiizumi-Gairani, Hiroshi Okuda, Aya Kobayashi, Misako Watabe, Sudha K. Pai, Puspa R. Pandey, Fei Xing, Koji Fukuda, Vishnu Modur, Shigeru Hirota, Kazuyuki Suzuki, Toshimi Chiba, Masaki Endo, Tamotsu Sugai, and Kounosuke Watabe. (2011) KAI1 is engaged in NDRG1-mediated metastasis suppression in human prostate cancer. J. Biol. Chem. 286; 18949. PubMed link
    • Fei Xing, Hiroshi Okuda, Misako Watabe, Aya Kobayashi, Sudha K. Pai, Wen Liu, Puspa R. Pandey, Koji Fukuda, Shigeru Hirota, Tamotsu Sugai, Go Wakabayshi, Keisuke Koeda, Masahiro Kashiwaba, Kazuyuki Suzuki, Toshimi Chiba, Masaki Endo and Kounosuke Watabe.(2011) Hypoxia-induced Jagged2 promotes breast cancer metastasis and self-renewal of cancer stem-like cells. Oncogene. 30, 4075-4086. PubMed link
    • Puspa R. Pandey, Hiroshi Okuda, Misako Watabe, Sudha K. Pai, Wen Liu,Aya Kobayashi, Fei Xing, Koji Fukuda, Shigeru Hirota, Tamotsu Sugai, Go Wakabayashi, Keisuke Koeda, Masahiro Kashiwaba, Kazuyuki Suzuki, Toshimi Chiba, Masaki Endo ,Tomoaki Fujioka, Susumu Tanji, Yin-Yuan Mo, Deliang Cao, Andrew C. Wilber and Kounosuke Watabe. (2011) Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase. Breast Can. Res. and Treatment. 130(2):387-98. PubMed link
    • Bandyopadhyay, S., Zhan, R., Chaudhuri, A., Watabe, M., Pai, S.K., Hirota, S., Hosobe, S.,Tsukada,T., Miura,K., Takano,Y., Saito,K., Pauza,M.E., Hayashi,S., Wang,Y., Mohinta,S., Mashimo,T., Iiizumi. M., Furuta, E. and Watabe, K. (2006) Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression. Nature Medicine, 12(8), 933-8. PubMed link