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异型盒基因表达异常的角度来研究肿瘤侵袭和转移的机制。我们以前发现同源异型盒基因HOXD 3的过表达可使人肺癌A5 49细胞向运动性、侵袭性和转移性细胞转化。我们还揭示了转移相关基因如整合素β 3、MMP-2、uPA和E-cadherin在过表达HOXD 3基因的A549细胞中的表达改变。在这项研究中，我们研究了HOXD 3基因下游转移相关基因网络中细胞粘附分子的作用。我们从这项研究中获得了以下结果。1)HOXD 3过表达对A549细胞运动性的增强依赖于整合素α v β 3，（2）HOXD 3过表达改变的30个基因中，有15个基因的表达同样受到整合素α v β 3信号的影响; 3）HOXD 3-过表达将潜伏的TGF-β转化为活性TGF-β，其通过TGF-β激活sigunaling途径。TGF-β刺激A549细胞向I型胶原的体外侵袭和迁移; 5）TGF-β诱导了30个转移相关基因中9个的相似表达模式，这些基因的表达被HOXD 3过表达改变。

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。

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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。