PTP1B在食管癌早期诊断中的作用及其机制研究

Metastasis is responsible for poor prognosis of esophageal squamous cell carcinoma (ESCC). However, the molecular mechanism of metastasis is not well understood. In our previous study, we found that PTP1B was up-regulated in ESCC tissues, especially in the early stage. PTP1B overexpression was correlated with poor prognosis in patients with ESCC. The results also showed that knockdown of PTP1B suppressed migration and invasion of ESCC cells and reduced activity of ERK. Basis on the preliminary findings, we will further investigate the mechanism of PTP1B promoting invasion and migration through ERK, and also screen biomarkers for detection of metastasis in the early stage of ESCC. This project will contribute to expound molecular mechanisms of ESCC metastasis, and also provide candidate molecular targets for the early iagnosis and therapy of ESCC.

肿瘤转移是导致食管癌预后差的重要原因，但肿瘤转移的分子机制尚不明确。我们最近研究发现蛋白酪氨酸磷酸酶1B（PTP1B）在食管癌组织中高表达，且其高表达与食管癌患者预后不良正相关，特别是其在早期食管癌组织中也存在异常高表达，提示可能是早期事件。体外实验结果显示，敲降PTP1B表达显著抑制食管癌细胞侵袭迁移能力，并且降低细胞外调节蛋白激酶ERK的磷酸化水平。本项目拟在前期发现的基础上，综合利用细胞系、动物模型以及临床标本，深入研究ERK介导PTP1B促进食管癌细胞侵袭迁移的分子机制，重点回答PTP1B如何调控ERK的磷酸化，还通过哪些特定的作用底物及调控蛋白影响食管癌细胞的侵袭迁移？PTP1B及其相关分子哪些有可能用于早期阶段食管癌转移判断？本项目的实施将有助于阐明PTP1B及其相关分子促进食管癌转移的理论基础，为深入理解食管癌发生发展的分子机制并为该病的早诊早治提供新的思路和方法。