端粒酶与肿瘤恶性行为密切相关。我们前期证实hTERT表达增强肿瘤转移。上一基金发现hTERT通过下调JAM-A来降低肿瘤细胞间紧密连接、同时上调Integrinβ1来增强肿瘤细胞与基质的粘附。这种粘附功能的同时改变是促进肿瘤细胞脱离原发灶侵入基底膜和血管膜的潜在机制。预实验提示机制可能为hTERT可能通过内源性siRNA下调JAM-A，而JAM-A则通过形成CD9三聚物对Integrinβ1负调控。本课题采用Co-IP，GST-Pull down，IP-RT-PCR、RdRP及动物模型，详细研究hTERT通过调控下游JAM-A和Integrinβ1来改变细胞不同极性粘附功能的机制。为端粒酶在肿瘤中的非端粒延长作用提供新的资料。

Human telomerase plays a key role in malignant tumor biology by employing its non-telomere elongation function. Our previous study has shown that hTERT expression up-regulate cell adhesion with ECM. Funded by our last NSFC grant, we fund that hTERT expression down-regulate the expression and function of tight junction protein JAM-A by a siRNA-involved mechanism, resulting in decreased cell-cell adhesion. More over JAM-A down-regulate the function of integrinβ1 by a CD9-mediated negative trisome mechanism, resulting in increased cell-matrix adhesion. The change of cell adhesion in both mechanism allow cells to detach the tumor mass and move towards basement membrane and blood vessel membrane, which was recognized as one of the earliest traits gained by metastating cells. Here we plan to employ Co-IP，GST-Pull down，IP-RT-PCR、RdRP function test to study the mechanism laid behind hTERT, JAM-A and integrinβ1. This study allow us further understanding of non-canonical function of telomerase in human cancer.