PRR11与Vimentin相互作用诱发肺癌细胞核纤层不稳定的机制研究

PRR11是我们自主发现的一个新基因，已证实其参与细胞周期尤其是有丝分裂的调节，其在肺癌中高表达并参与肺癌发生发展。研究结果已相继发表于IJBCB和BBRC，且已申请两项国家发明专利。最近我们又发现：PRR11与中间丝蛋白Vimentin存在相互作用；过表达PRR11可导致肺癌细胞Vimentin组装紊乱，并由此诱发核纤层不稳定和染色质早熟凝聚现象。我们由此提出“PRR11通过Vimentin诱发核纤层不稳定而促进肺癌发生发展”的学术假想。本项目拟在前期系列研究的基础上，采用Co-IP、GST pull-down、间接免疫荧光等多种分子细胞生物学技术，鉴定PRR11与Vimentin相互作用关系，并进而阐明PRR11通过Vimentin诱发肺癌细胞核纤层不稳定的分子机制与临床意义。本研究不仅将丰富肿瘤细胞生物学基础理论，而且也将为探讨基于PRR11的肺癌分子诊断与靶向治疗奠定基础。

Proline-rich protein 11 (PRR11) is a novel tumor-related gene identified by our group. We have demonstrated that PRR11 palys pivotal roles in both cell cycle progression and lung cancer development (Ji et al 2013; Zhang et al 2015). We have also applied for two related patents regarding this novel gene. Recently, we further found that PRR11 interacts with the classic intermediate filament protein, vimentin, and overexpression of PRR11 induces vimentin disassembly and subsequently leads to nuclear lamina disassembly and premature chromatin condensation in lung cancer cells. These data strongly suggest that PRR11 induces nuclear lamina disassembly though interaction with vimentin and hence contributes to lung cancer development. In the present study, we will utilize a series of classic molecular and cellular techniques including Co-IP, GST pull-down, indirect immunofluorescence assay etc, to identify the interaction of PRR11 with vimentin, and investigate the molecular mechanisms and clinical significances of PRR11 induced nuclear lamina disassembly though interaction with vimentin in lung cancer cells. This study will not only extend our current knowledge of cancer cell behaviors, but also provide rationale for exploring PRR11-based diagnostic and therapeutic strategies in lung cancer.