Functional analysis of a novel signal molecule CDCP1 which regulates anchorage-independent growth in cancer cells

调节癌细胞贴壁依赖性生长的新型信号分子CDCP1的功能分析

• 批准号: 21590350
• 负责人: UEKITA Takamasa
• 金额: $ 3万
• 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 (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590350/
• 关键词: CDCP1; 足場非依存性; 細胞運動能; 浸潤; MMP; 足場非依存性増殖; がんの浸潤; 細胞間接着

In this study, we found the three functions of CDCP1 in cancer cells. First, CUB2 and CUB3 in the extracellular domain of CDCP1 and the region including Tyrosine734 in the intracellular domain of CDCP1 might contribute to regulate anchorage-independent growth in cancer cell. Second, CDCP1 regulates cancer invasion through regulation of MMP-9 secretion and membranous transportation of MT1-MMP to invadopodia. Finally, induction of CDCP1 expression by Ras along with tyrosine phosphorylation of CDCP1 by Src family kinases is required for Ras-mediated oncogenic phenotypes, such as anchorage-independent growth, invasion and metastasis.

在这项研究中，我们发现了CDCP1在癌细胞中的三个功能。首先，CDCP1胞外域中的CUB2和CUB3以及CDCP1胞内域中包括酪氨酸734的区域可能有助于调节癌细胞的锚定非依赖性生长。其次，CDCP1通过调节MMP-9分泌和MT1-MMP向侵袭伪足的膜运输来调节癌症侵袭。最后，Ras 诱导 CDCP1 表达以及 Src 家族激酶对 CDCP1 进行酪氨酸磷酸化，这对于 Ras 介导的致癌表型（如贴壁依赖性生长、侵袭和转移）是必需的。

项目成果

肺がんの骨転移モデル作製と骨転移関連因子の探索

肺癌骨转移模型的建立及骨转移相关因素的寻找

• 发表时间: 2010
• 作者: 八木玲子;上北尚正;堺隆一
• 通讯作者: 堺隆一

CDCP1は膵癌の転移・浸潤能に関わる予後因子である

CDCP1是与胰腺癌转移和侵袭能力相关的预后因素

• 发表时间: 2009
• 作者: Lefter LP;Dima S;Sunamura M;Furukawa T;Sato Y;Abe M;Chivu M;Popescu I;Horii A;上北尚正
• 通讯作者: 上北尚正

Regulation of metastasis and invasion by a novel Src substrate CDCP1

新型Src底物CDCP1对转移和侵袭的调节

• 发表时间: 2009
• 作者: 上北尚正;堺隆一;Uekita T. and Sakai R
• 通讯作者: Uekita T. and Sakai R

CUB Domain-Containing Protein 1, a Prognostic Factor for Human Pancreatic Cancers, Promotes Cell Migration and Extracellular Matrix Degradation

• DOI: 10.1158/0008-5472.can-10-0220
• 发表时间: 2010-06-15
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Miyazawa, Yuri;Uekita, Takamasa;Sakai, Ryuichi
• 通讯作者: Sakai, Ryuichi

CDCP1 links Ras and Src signaling pathway as a common effector for the promotion of tumor metastasis

CDCP1连接Ras和Src信号通路作为促进肿瘤转移的共同效应器

• 发表时间: 2011
• 作者: Takamasa Uekita;Ryuichi Sakai;Uekita T. and Sakai R
• 通讯作者: Uekita T. and Sakai R