端锚聚合酶1在肿瘤演进及治疗领域研究进展

Role of Telomerase I in Cancer Progression and Treatment

由于端粒酶是永生化细胞和绝大多数肿瘤细胞持续分裂增殖的必要条件,因此阻滞端粒酶表达及其活性成为肿瘤治疗的作用靶点,但研究证实仅阻滞端粒酶的活性还不能达到抗肿瘤的理想效果。近期研究发现了肿瘤端粒长度的正调控因子-Tankyrase 1(TANK1),它与端粒延长的抑制因子一端粒结合蛋白Ⅰ(TRF1)共同作用使端粒维持在一特定长度,保证了肿瘤细胞持续生长繁殖。TANK1的发现成为联系端粒酶与TRF1作用的桥梁,由于该酶是调控端粒复制中最为明确的一环,因此成为细胞癌变、肿瘤演进及癌症靶标治疗的新热点。现对TANK1作为分子靶器在肿瘤发生、演进中的作用机制及其在肿瘤治疗领域中的研究进展进行综述。

We propose that the upregulated expression and activation of telomerase is the necessary condition for the proliferation of immortalizing cells. For most cancers, this enzyme is a potentially useful target for therapeutic intervention. But it is now clear that simply inhibiting telomerase may not result in the anti-cancer effects that were originally hypothesized. Recently, scientists have discovered a positive regulator of the telomere, named Tankyrase 1 （TANK1）. With the balance between the positive regulation of TANK1 and the negative regulation of TRF1, the length of the telomere is maintained at a constant. The discovery of TANK1 provides a bridge between telomerase and TRF1. Since the function of TANK1 has already been defined in the process of telomere replication, it has become a hot topic in the mechanism of canceration and gene therapy. This article reviews the mechanism of TANK1 in oncogenesis and cancer progression and discusses its value in cancer therapy.