The roles of cell adhesion molecules in the metastasis-related gene network downstream of HOXD3 gene

HOXD3基因下游转移相关基因网络中细胞粘附分子的作用

• 批准号: 13470048
• 负责人: HAMADA Jun-ichi
• 金额: $ 8.77万
• 依托单位: HOKKAIDO UNIVERSTY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470048/
• 关键词: homeobox gene; HOXD3; metastasis; TGF-beta; integrin beta3; invasion; motility; TGF-Β; 遺伝子発現; 細胞接着因子; インテグリン

We have been studying the mechanisms of tumor invasion and metastasis from the viewpoint of abnormal expression of homeobox genes by tumor cells. We previously found that the overexpression of HOXD3 gene, one of the homeobox genes converted human lung cancer A5 49 cells into more motile, invasive and metastatic ones. We also revealed the altered expressions of metastasis-related genes such as integrin beta3, MMP-2, uPA and E-cadherin in A549 cells overexpressing HOXD3 gene. In this study, we examined the roles of cell adhesion molecules in the metastasis-related gene network downstream of the HOXD3 gene. We obtained the following results from this study. 1) Enhanced motility of A549 cells by the HOXD3-overexpression was dependent on integrin alphavbeta3 ; 2) the expressions of 15 of 30 genes of which expressions were altered by the HOXD3-overexpression were similarly changed by the signals through integrin alphavbeta3 ; 3) the HOXD3-overexpression converted latent TGF-beta into active one which activated the sigunaling pathways through TGF-beta receptors in an autocrine manner ; 4) TGF-beta stimulated the in vitro invasion and migration of A549 cells to type I collagen ; 5) TGF-beta induced the similar expression patterns in 9 of 30 metastasis-related genes of which expressions were altered by the HOXD3-overexpression.

我们一直从肿瘤细胞同源盒基因异常表达的角度研究肿瘤侵袭转移的机制。我们之前发现，同源盒基因之一HOXD3基因的过表达可将人肺癌A5 49细胞转化为更具运动性、侵袭性和转移性的细胞。我们还发现，在过表达HOXD3基因的A549细胞中，整合素β 3、MMP-2、uPA和E-cadherin等转移相关基因的表达发生了改变。在这项研究中，我们研究了细胞粘附分子在HOXD3基因下游转移相关基因网络中的作用。我们从这项研究中得到了以下结果。1) hoxd3过表达对A549细胞运动的增强依赖于整合素alphavbeta3；2) 30个被hoxd3过表达改变的基因中，有15个基因的表达同样被整合素alphavbeta3的信号改变；3) hoxd3过表达将潜伏的tgf - β转化为活跃的tgf - β，以自分泌方式激活tgf - β受体的信号通路；4) tgf - β刺激A549细胞向I型胶原的体外侵袭和迁移；5)在hoxd3过表达改变的30个转移相关基因中，tgf - β诱导的9个基因表达模式相似。

项目成果

Miyazaki, Y.J.: "HOXD3 enhances motile and invasive activities through the TGf-beta-dependent and -independent pathways in A549 cells"Oncogcne. 21. 798-808 (2002)

Miyazaki, Y.J.：“HOXD3 通过 A549 细胞中 TGf-β 依赖性和非依赖性途径增强运动和侵袭活性”Oncogcne。

Matsumoto J: "Differential Mechanisms of Constitutive Akt/PKB Activation and Its Influence on Gene Expression in pancreatic Cancer Cells"Jpn J Cancer Res. 93. 1317-1326 (2002)

松本 J：“组成型 Akt/PKB 激活的不同机制及其对胰腺癌细胞基因表达的影响”Jpn J Cancer Res。

Kitajo, H.: "Rho regulates the hepatocyte growth factor/scatter factor-stimulated cell motility of human oral squamous cell carcinoma cells"Oncol. Rep.. in press.

Kitajo, H.：“Rho 调节人口腔鳞状细胞癌细胞的肝细胞生长因子/散射因子刺激的细胞运动”Oncol。

Kitajo, H.: "Rho regulates the hepatocyte gowth factor/scatter factor-stimulated cell motility of human oral squamous cell carcinoma cells"Oncol. Rep.. (印刷中). (2002)

Kitajo, H.：“Rho 调节人口腔鳞状细胞癌细胞的肝细胞生长因子/分散因子刺激的细胞运动”Oncol.（出版中）。

Hamada, J.: "Overexpression of homeobox gene HOXD3 induces coordinate expression of metastasis-related genes in human lung cancer cells"Int. J. Cancer. 93. 516-525 (2001)

Hamada, J.：“同源框基因 HOXD3 的过度表达诱导人肺癌细胞中转移相关基因的协调表达”Int。