Masuda, Kenta



School of Medicine, Department of Obstetrics and Gynecology (Shinanomachi)




Papers 【 Display / hide

  • An evolving story of the metastatic voyage of ovarian cancer cells: cellular and molecular orchestration of the adipose-rich metastatic microenvironment

    Motohara T., Masuda K., Morotti M., Zheng Y., El-Sahhar S., Chong K., Wietek N., Alsaadi A., Karaminejadranjbar M., Hu Z., Artibani M., Gonzalez L., Katabuchi H., Saya H., Ahmed A.

    Oncogene (Oncogene)  38 ( 16 ) 2885 - 2898 2019.04

    ISSN  09509232

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    © 2018, The Author(s). Metastasis is a complex multistep process that involves critical interactions between cancer cells and a variety of stromal components in the tumor microenvironment, which profoundly influence the different aspects of the metastatic cascade and organ tropism of disseminating cancer cells. Ovarian cancer is the most lethal gynecological malignancy and is characterized by peritoneal disseminated metastasis. Evidence has demonstrated that ovarian cancer possesses specific metastatic tropism for the adipose-rich omentum, which has a pivotal role in the creation of the metastatic tumor microenvironment in the intraperitoneal cavity. Considering the distinct biology of ovarian cancer metastasis, the elucidation of the cellular and molecular mechanisms underlying the reciprocal interplay between ovarian cancer cells and surrounding stromal cell types in the adipose-rich metastatic microenvironment will provide further insights into the development of novel therapeutic approaches for patients with advanced ovarian cancer. Herein, we review the biological mechanisms that regulate the highly orchestrated crosstalk between ovarian cancer cells and various cancer-associated stromal cells in the metastatic tumor microenvironment with regard to the omentum by illustrating how different stromal cells concertedly contribute to the development of ovarian cancer metastasis and metastatic tropism for the omentum.

  • Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation

    Zheng Y., Sethi R., Mangala L., Taylor C., Goldsmith J., Wang M., Masuda K., Karaminejadranjbar M., Mannion D., Miranda F., Herrero-Gonzalez S., Hellner K., Chen F., Alsaadi A., Albukhari A., Fotso D., Yau C., Jiang D., Pradeep S., Rodriguez-Aguayo C., Lopez-Berestein G., Knapp S., Gray N., Campo L., Myers K., Dhar S., Ferguson D., Bast R., Sood A., Von Delft F., Ahmed A.

    Nature Communications (Nature Communications)  9 ( 1 )  2018.12

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    © 2018 The Author(s). Though used widely in cancer therapy, paclitaxel only elicits a response in a fraction of patients. A strong determinant of paclitaxel tumor response is the state of microtubule dynamic instability. However, whether the manipulation of this physiological process can be controlled to enhance paclitaxel response has not been tested. Here, we show a previously unrecognized role of the microtubule-associated protein CRMP2 in inducing microtubule bundling through its carboxy terminus. This activity is significantly decreased when the FER tyrosine kinase phosphorylates CRMP2 at Y479 and Y499. The crystal structures of wild-type CRMP2 and CRMP2-Y479E reveal how mimicking phosphorylation prevents tetramerization of CRMP2. Depletion of FER or reducing its catalytic activity using sub-therapeutic doses of inhibitors increases paclitaxel-induced microtubule stability and cytotoxicity in ovarian cancer cells and in vivo. This work provides a rationale for inhibiting FER-mediated CRMP2 phosphorylation to enhance paclitaxel on-target activity for cancer therapy.

Papers, etc., Registered in KOARA 【 Display / hide

Research Projects of Competitive Funds, etc. 【 Display / hide

  • 卵巣癌の微小残存病変に対する解析研究


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 増田 健太, Grant-in-Aid for Early-Career Scientists , Principal Investigator