Livin-Fibronectin分子与生物力学信号偶联介导前列腺癌“抵抗-逃离”转移机制的研究

项目名称： Livin-Fibronectin分子与生物力学信号偶联介导前列腺癌“抵抗-逃离”转移机制的研究

项目编号： No.81202030

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 杨德勇

作者单位： 大连医科大学

项目金额： 23万元

中文摘要： 侵袭与转移是前列腺癌的主要致死因素之一。我们前期研究发现，凋亡抑制蛋白Livin可以通过调节细胞外力学信号感受器-Fibronectin的表达直接参与调节前列腺癌的侵袭转移能力，提示Livin以及Fibronectin分子可能偶联细胞外力学信号，介导前列腺癌"抵抗-逃离"式侵袭、转移行为，但其具体机制不明。本项研究中，我们拟（1）通过对前列腺癌临床标本研究，分析前列腺癌组织硬度与Livin基因表达以及前列腺癌临床、病理特征的相关性。（2）通过灌流式细胞体外3-D培养，研究细胞外力学环境（细胞外基质硬度以及细胞承受外部压力）对Livin基因表达及细胞运动、侵袭能力的影响。（3）探讨Livin调节Fibronectin进而增加细胞外生物力学信号传递，激活肿瘤细胞内侵袭、转移相关分子信号的具体机制。从生物力学与分子生物学角度理解前列腺癌的侵袭、转移行为，为寻找前列腺癌的治疗新策略提供理论基础。

中文关键词： 前列腺癌；生物力学性质；细胞外基质；I型胶原纤维；力学信号传导

英文摘要： Invasion and metastasis is a major risk factor for prostate cancer mortality. According to the results discovered through our previous study apoptosis inhibitor protein Livin is an entity regarded as a facor directly involved in regulating prostate cancer metastasis by regulating the expression of the extracellular mechanical receptor-Fibronectin. Thus we speculated that Livin and Fibronectin molecules can couple extracellular biomechanical signals in order to mediate prostate cancer "resistance-flee" invasion and metastasis behavior however,exact mechanism is unknown. In our prospective study we undermine couple of maneuvers for getting deep into the molecular and biomechanical basis for prostatic carcinoma which are: (1) we analyze the correlation among prostate cancer tissue stiffness, Livin gene expression, and prostatic cancer clinical and pathological features through clinical samples. (2)By 3-D in-vitro cell culture investigation, the tumour cell foci is effected by biomechanical entitiy like extracellular matrix stiffness and the tumour cell compression because of ECM fibrosis furnishes Livin gene expression which directly or indirectly has a profound impression on invasion and metastasis of cancer cells.(3)As a result of apoptotic stress which indirectly flourishes Livin protein and causes build up of i

英文关键词： prostate cancer；mechanical property；Extracellular matrix；collagen I；mechanotransduction signal pathway