Basic studies on TOPK as a target molecule of cancer

TOPK作为癌症靶分子的基础研究

• 批准号: 20590401
• 负责人: ABE Yasuhito
• 金额: $ 2.58万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590401/
• 关键词: TOPK; 乳癌; 増殖; 悪性度; 腫瘍; シグナル

Purpose: A MAPKK-like mitotic protein kinase, TOPK, plays a pivotal role in the growth and movement of cancer cells. As is evidenced by clinical application of anti-HER2-monoclonal antibody, EGF-R/HER2 mediates an important signaling in the proliferation and invasion of breast cancer cells through MAPK- and PI3K- signaling. Raf, an imperative member of MAPK signaling, binds to TOPK, although, significance of this interaction has not been elucidated. In this study, we analyzed expression of TOPK and investigated biological significance of TOPK-Raf interaction using breast cancer cells.Experimental Design: We analyzed the expression of TOPK in the clinical breast cancer tissues and investigated MAPK-signaling from the aspect of TOPK and Raf in breast cancer cells.Results: Immunohistochemical analysis revealed that the peak-expression intensity of TOPK correlated with the Histologic Grade of human invasive ductal carcinoma of breast. Our results suggested that Raf phosphorylates TOPK at Thr-198, a critical residue for kinase activity of TOPK and that TOPK enhances MAPK signaling by upregulating Ras binding to Raf.Conclusions: TOPK is indicated to play an important role in the malignant potential of breast cancer via EGF-R/HER2 signaling. This study suggests that TOPK can be a molecular target for breast cancer therapy in the future.

目的：MAPKK样有丝分裂蛋白激酶（TOPK）在肿瘤细胞的生长和运动中起关键作用。抗HER 2单克隆抗体的临床应用证明，EGF-R/HER 2通过MAPK-和PI 3 K-信号传导介导乳腺癌细胞增殖和侵袭的重要信号传导。Raf是MAPK信号传导的重要成员，与TOPK结合，但这种相互作用的意义尚未阐明。在本研究中，我们分析了TOPK在乳腺癌细胞中的表达，并探讨了TOPK-Raf相互作用的生物学意义。实验设计：我们分析了TOPK在临床乳腺癌组织中的表达，并从TOPK和Raf在乳腺癌细胞中的角度研究了MAPK信号通路。免疫组化分析显示TOPK的表达强度与乳腺浸润性导管癌的组织学分级有关。我们的研究结果表明，Raf磷酸化TOPK在Thr-198，一个关键的残基激酶活性的TOPK和TOPK增强MAPK信号通过上调Ras结合Raf.Conclusions：TOPK是指发挥重要作用，在乳腺癌的恶性潜能通过EGF-R/HER 2信号。本研究提示TOPK可能成为未来乳腺癌治疗的分子靶点。

项目成果

Neither MafA/L‐Maf nor MafB is essential for lens development in mice

• DOI: 10.1111/j.1365-2443.2009.01321.x
• 发表时间: 2009-08
• 期刊: Genes to Cells
• 影响因子: 2.1
• 作者: T. Takeuchi;T. Kudo;K. Ogata;Michito Hamada;Megumi Nakamura;K. Kito;Y. Abe;Norifumi Ueda;Masayuki Yamamoto;J. D. Engel;Satoru Takahashi

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis.

血清抗 PDIK1L 自身抗体作为子宫内膜异位症的新型标志物。

• DOI: 10.1016/j.fertnstert.2010.03.008
• 发表时间: 2010
• 期刊: Fertility and sterility
• 影响因子: 6.7
• 作者: M. Nabeta;Y. Abe;Ryuma Haraguchi;K. Kito;Y. Kusanagi;Masaharu Ito
• 通讯作者: Masaharu Ito

ADP-ribosylation factor like 7(ARL7)interacts with α-tubulin and modulates intracelluar vesicular transport

ADP-核糖基化因子 7 (ARL7) 与 α-微管蛋白相互作用并调节细胞内囊泡运输

• 发表时间: 2009
• 期刊: Biochemical and Biophysical Research Communications 384
• 作者: Wei;et al.
• 通讯作者: et al.