Regulation of adhesion and migration of cancer cells by tyrosine kinase signaling

通过酪氨酸激酶信号调节癌细胞的粘附和迁移

• 批准号: 17014086
• 负责人: SAKAI Ryuichi
• 金额: $ 29.95万
• 依托单位: National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17014086/
• 关键词: 転移・浸潤; 足場非依存性; Srcファミリーキナーゼ; CDCP1; チロシンリン酸化; Ossa; 酸化ストレス; スキルス胃がん; 運動能; 腸間膜播種; Srcキナーゼ; Cortactin; p130Cas; 細胞接着; チロシンキナーゼ; Srcファミリー; pl30Cas; 細胞運動能; ephrin-B1; paxillin; ShcC; 神経芽腫; 転移・浸潤能

In this project, numbers of proteins which are tyrosine-phosphorylated during the malignant progression of cancers were identified and functional analysis was performed. CDCP1, which was identified as a molecule involved in anchorage independent growth of cancer cells, also regulates cell migration and matrix degradation. A subset of lung and pancreatic tumors which has high levels of CDCP1 expression showed statistically worse prognosis than that with low levels of CDCP1 expression in clinical samples. It was demonstrated that ephrin-B1 controls multiple factors associated with metastasis such as cell-cell interaction and migration, and peptides which block ephrin-B1 signaling suppressed the peritoneal dissemination of gastric cancers in vivo. A novel protein Ossa identified as a molecule tyrosine-phosphorylated during peritoneal dissemination was shown to be essential for acquireing resistance to the oxidative stress-induced apoptosis.

在该项目中，鉴定了在癌症恶性进展过程中酪氨酸磷酸化的大量蛋白质并进行了功能分析。 CDCP1 被确定为参与癌细胞贴壁独立生长的分子，还调节细胞迁移和基质降解。在临床样本中，具有高CDCP1表达水平的肺和胰腺肿瘤子集表现出比CDCP1低表达水平的预后更差的预后。研究表明，ephrin-B1 控制与转移相关的多种因素，例如细胞间相互作用和迁移，并且阻断 ephrin-B1 信号传导的肽可抑制体内胃癌的腹膜播散。一种新的蛋白质 Ossa 被鉴定为腹膜传播过程中酪氨酸磷酸化的分子，它对于获得对氧化应激诱导的细胞凋亡的抵抗力至关重要。

项目成果

癌遺伝子Srcの下流因子p130CasのC末端断片化のがん化及びがん転移における意義

癌基因Src下游因子p130Cas C端片段化在癌变和癌症转移中的意义

• 发表时间: 2009
• 作者: Kaneko N;Miura K;Gu Z;Karasawa H;Ohnuma S;Sasaki H;Tsukamoto N;Yokoyama S;Yamamura A;Nagase H;Shibata C;Sasaki I;Horii A;澤井勇一郎
• 通讯作者: 澤井勇一郎

Biological role of anaplastic lymphoma kinase in neuroblastoma

• DOI: 10.1016/s0002-9440(10)62966-5
• 发表时间: 2005-07-01
• 期刊: AMERICAN JOURNAL OF PATHOLOGY
• 影响因子: 6
• 作者: Osajima-Hakomori, Y;Miyake, I;Sakai, R
• 通讯作者: Sakai, R

Phosphatidylinositol 4,5-bisphosphate and PIP5-kinase Iα are required for invadopodia formation in human breast cancer cells

人乳腺癌细胞侵袭伪足的形成需要磷脂酰肌醇 4,5-二磷酸和 PIP5 激酶 Iα

• 发表时间: 2010
• 期刊: Cancer Sci. (In press)
• 作者: 芝崎 太;内野博之;Tanaka M;Yamaguchi H
• 通讯作者: Yamaguchi H

CUB domain-containing protein 1 is a novel regulator of anoikis resistance in lung adenocarcinoma

含 CUB 结构域的蛋白 1 是肺腺癌失巢凋亡抵抗的新型调节因子

• 发表时间: 2007
• 期刊: Mol. Cell. Biol. 27
• 作者: Uekita;T.;Jia;L.;Narisawa-Saito;M.;Yokota;J.;Kiyono;T.;Sakai;R.
• 通讯作者: R.

Tyrosine phosphorylation of paxillin affects the metastatic potential of human osterosarcoma

桩蛋白酪氨酸磷酸化影响人骨肉瘤的转移潜力

• 发表时间: 2005
• 期刊: Oncogene 24巻
• 作者: Azuma;K.
• 通讯作者: K.