Identification of Tumor Metastasis Suppressor Genes

The existence of tumor metastasis suppressor genes was long been predicted and they were expected to suppress only metastatic process but not tumor initiation. We identified several chromosomal regions of metastasis suppression in prostate and breast cancers. We also clarified the function of two key metastasis suppressor genes, KAI1 and NDRG1, their signaling pathways and mechanism by which they cross-talk each other. We then showed several small molecules that potentially activate these genes and suppress recurrence.

Selected publications

Mashimo, T., Watabe, M., Hirota, S., Hosobe, S., Tagtmeyer, P., Rinker-Schaeffer, C. and Watabe, K. (1998). The expression of the KAI1 gene, a tumor metastasis suppressor, is directly activated by P53. Proc. Natl. Acad. Sci. USA. 95, 11307-11311

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 Med. 12, 933-9388

Bandyopadhyay, S., Wang, Y., Zhan, R., Pai, S.K., Watabe, M., Iiizumi, M., Furuta, E., Mohinta, S., Liu, W., Hirota, S., Hosobe, S., Tsukada, T., Miura, K., Takano, Y., Saito, K., Commes, T., Piquemal, D., Hai, T., and Watabe, K. (2006) The tumor metastasis suppressor gene Drg-1 down regulates the expression of ATF3 in prostate cancer. Cancer Res. 66(24),11983-90

Liu, W., Iiizumi-Gairani, M., Okuda, H., Watabe, M., Pai, S.K., Pandey, P.R., Hirota, S., Xing, F., Kobayashi, A., Mo, Y.-Y. Fukuda, K., Li, Y., and Watabe, K. (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