Elucidation of Ciz-RANKL signaling mechanism and search for novel therapeutic target molecules for cancer bone metastasis.

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K11719
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Tokyo Medical and Dental University (2016-2017, 2019); Tsurumi University (2018)
• Principal Investigator: Sakuma Tomomi 東京医科歯科大学, 歯学部附属病院, 医員 (70633733)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: Ciz / 腫瘍転移能 / RANKL / 悪性度 / ポドソーム

Outline of Final Research Achievements

From the comparison between the malignant melanoma cell line B16 and B16F10, which has high metastatic potential.The role of Ciz on tumor cell migration and adhesion and RANKL was examined.In addition, we analyzed the expression level of Ciz in other tumor cells at the RNA and protein levels, and proceeded to verify whether differences in the expression level and properties were observed as in malignant melanoma depending on the difference in malignancy.
Although Ciz is presumed to be involved in cytoskeletal regulation and survival maintenance via the Ras / MEK / MAPK pathway, protein levels of ERK1 / 2, MAPK, p130cas, and phosphorylated p130cas in Ciz knockdown and forced expression cells were estimated. Analysis was performed to clarify the effect of Ciz expression.Focusing on cell adhesion and migration, we analyzed changes over time in podosome expression depending on the migration stage on the adhesion surface of tumor cells.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

本研究はCiz（Cas Interacting Zinc Finger Protein)発現の寄与を検証しCiz－RANK（NFｋB 活性化受容体リガンド）関係シグナルの分子機序を解明し、骨転移に関する新たなメカニズムを解明し、その予防や治療の創薬の標的開発・同定を目的とした。
腫瘍細胞の悪性度の違いと、Ciz発現量の関連を悪性黒色腫だけでなく他の細胞でも検証することにより、腫瘍細胞の骨転移のメカニズムの要所である、細胞の遊走性と接着性のメカニズムを解明する一助となる知見を示せた。また、さらなるターゲットとしてポドソームの発現変化の検証は今後さらに本研究の意義を興味深いものにしていけると考える。