PTPN18在乳腺癌发生、发展及预后治疗中的作用及分子机制

Protein tyrosine phosphatase non-receptor type 18(PTPN18) is an important regulator.The N-terminal catalytic domain and the C-terminal PEST domain of PTPN18 can regulate phosphorylation and protein levels of HER2. Moreover the HER2/PTPN18 ratio was positive correlated with breast cancer stage. However whether PTPN18 can regulate other HER2 phosphorylation sites and the exact regulation mechanism are not known yet. Our previous work showed PTPN18 indeed could specifically dephosphorylate HER2 at pY(1221) site. We also demonstrated the dynamic process of how PTPN18 dephosphorylated its substrates by using structure biology technique. In this project, we want to investigate the function of PTPN18 and the role of PTPN18 and HER2 in the development of breast cancer by combination of molecular biology, cell biology, and structure biology technique from protein level, cell level, animal model level and human breast cancer tissue level.

蛋白酪氨酸磷酸酶PTPN18是重要的细胞调控因子。PTPN18 N端的催化结构域和C末端的PEST结构域分别调节HER2的磷酸化水平和蛋白水平。并且HER2/PTPN18的蛋白表达量比值与乳腺癌的分期呈正相关。但是，PTPN18是否可以去磷酸化HER2的其他位点以及PTPN18具体催化机制还不清楚。我们的前期研究表明，PTPN18可以去磷酸化HER2的pY(1221)位点，而且同时我们用结构生物学手段阐明了PTPN18去磷酸化底物的动态过程。基于我们的前期研究，本课题将结合分子生物学，细胞生物学，结构生物学等手段在蛋白水平，细胞水平，动物模型以及人乳腺癌组织样本上研究PTPN18的功能以及进一步研究PTPN18和HER2在乳腺癌发生发展中的作用。