PIWIL2是一种新发现的多功能癌/睾丸蛋白，包括本课题组的已有研究显示PIWIL2在肿瘤细胞增殖、凋亡中具有重要的调控作用，但其在肿瘤细胞中的作用仍有待进一步阐明。近期我们发现PIWIL2能够对肿瘤细胞的细胞骨架系统进行调控。现有研究显示，细胞骨架与肿瘤细胞的恶性转化、细胞增殖、细胞周期和迁移侵袭密切相关，但对于肿瘤细胞中细胞骨架，尤其是微管系统异常变化的机理尚不清楚。我们前期初步研究发现，PIWIL2可以通过与TBCB作用对肿瘤细胞微管聚合/解聚产生影响。我们拟在此基础上进一步深入研究并阐明肿瘤细胞中PIWIL2及其剪接异构体PL2L60对TBCB的调控作用，并进一步影响TBCB下游微管聚合/解聚的分子机制，阐明PIWIL2通过调控TBCB及下游微管聚合调节肿瘤细胞增殖和迁移侵袭等方面新的功能机理。

PIWIL2, one member of Piwi/Ago proteins, belongs to a group of cancer/testis antigens and plays multiple functions in cellular process. Previous studies including ours have shown that PIWIL2 plays essential roles in the proliferation and apoptosis of tumor cells. However, the molecular mechanism underlying its functions in tumor cells remains largely unclear. Our recent work have shown that PIWIL2 is involved in regulating the cytoskeleton system, which is known to be highly associated with transformation, proliferation, cell cycle, migration and invasion ability of tumor cells. But the regulating mechanism that leads to the abnormity of the cytoskeleton, especially the microtubule in tumor cells requires further investigation. Only recently, we revealed that the interaction of PIWIL2 and tubulin folding cofactor B (TBCB) is involved in microtubule dynamics. To further investigate these underlying molecular mechanism in this study, a series of experiments such as immunoprecipitation, western blot, confocal-immunofluorescence and etc will be performed, and some specific cell lines and animal models will be constructed. We aim to clarify the mechanism that how PIWIL2 and its variant PL2L60 regulate TBCB and microtubule dynamics, which is involved in tumor cell proliferation and metastasis. This study will reveal some novel signaling pathways in which PIWIL2 is involved in tumor cells, providing new insights into the function of PIWIL2 and TBCB in the proliferation and metastasis of tumor cells.