HDPR1-δ-catenin通路在非小细胞肺癌侵袭和凋亡中的作用机制

项目名称： HDPR1-δ-catenin通路在非小细胞肺癌侵袭和凋亡中的作用机制

项目编号： No.81201853

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： 杨志强

作者单位： 温州医科大学

项目金额： 20万元

中文摘要： HDPR1是Wnt通路中重要的负向调节因子，参与许多肿瘤的发生发展。p120ctn家族主要包括：p120ctn、ARVCF、p0071和δ-catenin。p120ctn家族蛋白的核心作用是通过与E-cadherin近膜序列连接而稳定该蛋白，从而抑制细胞的侵袭。我们最近发现并报道：在肺癌细胞系中，干扰HDPR1的表达可通过下调p120ctn表达从而促进肺癌细胞的侵袭。但是，关于HDPR1与δ-catenin之间调控关系的研究国内外尚未见相关报道。本研究中，我们拟在组织学水平、细胞学水平和分子水平阐明HDPR1与δ-catenin的表达及相互调控关系，采用Transwell侵袭小室、细胞划痕实验、流式细胞术、TUNEL等方法检测HDPR1-δ-catenin通路对于肺癌侵袭、凋亡的影响。研究结果将为揭示肺癌侵袭转移和凋亡的机制提供新的视角，并为临床寻找新的有效防治靶点提供重要的理论依据。

中文关键词： 肺癌；HDPR1；δ-catenin；侵袭；凋亡

英文摘要： HDPR1 is an important negative regulator in Wnt signal pathway and is involved in many tumors development. p120ctn family mainly includes p120ctn, ARVCF, p0071 and δ-catenin. p120ctn family protein play a critical role in inhibiting cell invasion through connection and stabilization with juxtamembrane sequence of E-cadherin protein. We have recently discovered and reported that knockdown of HDPR1 could promote the invasiveness of lung cancer cells through down-regulating p120ctn expression. However, the relationship between HDPR1 and δ-catenin has not been reported. In this study, we will clarify the regulation relationship between HDPR1 and δ-catenin expression from histological, cytology and molecular levels, respectively. Transwell assay, cytometry scratches experiment, flow cytometry and TUNEL methods will be introduced to detect the influence of HDPR1-δ-catenin pathway on lung cancer cell apoptosis and invasiveness. The results will help us to provide new perspective on the invasion and metastasis of lung cancer and apoptosis mechanisms and to provide important theory basis for new clinical effective prevention and treatment targets.

英文关键词： lung cancer；HDPR1；δ-catenin；invasion；apoptosis