The reactivation of telomerase enables cancer cells to maintain the telomere length, bypassing replicative senescence and achieving cellular immortality. In addition to its canonical role in telomere maintenance, accumulating evidence highlights telomere-length-independent functions of TERT, the catalytic subunit of telomerase. These extratelomeric functions involve the regulation of signaling pathways and transcriptional networks, creating feed-forward loops that promote cancer cell proliferation, resistance to apoptosis, and disease progression. This review explores the complex mechanisms by which TERT modulates key signaling pathways, such as NF-κB, AKT, and MYC, highlighting its role in driving autonomous cancer cell growth and resistance to therapy in B-cell malignancies. Furthermore, we discuss the therapeutic potential of targeting TERT’s extratelomeric functions. Unlike telomere-directed approaches, which may require prolonged treatment to achieve effective telomere erosion, inhibiting TERT’s extratelomeric functions offers the prospect of rapid tumor-specific effects. This strategy could complement existing chemotherapeutic regimens, providing an innovative and effective approach to managing B-cell malignancies.
端粒酶的重新激活使癌细胞能够维持端粒长度，从而绕过复制性衰老并实现细胞永生。除了在端粒维持中的经典作用外，越来越多的证据表明端粒酶催化亚基TERT具有不依赖于端粒长度的功能。这些端粒外功能涉及信号通路和转录网络的调控，形成促进癌细胞增殖、抗凋亡和疾病进展的正反馈循环。本综述探讨了TERT调控关键信号通路（如NF-κB、AKT和MYC）的复杂机制，重点阐述了其在驱动B细胞恶性肿瘤中癌细胞自主生长和治疗抵抗中的作用。此外，我们讨论了靶向TERT端粒外功能的治疗潜力。与可能需要长期治疗才能实现有效端粒侵蚀的端粒导向方法不同，抑制TERT的端粒外功能有望实现快速的肿瘤特异性效应。这一策略可补充现有化疗方案，为B细胞恶性肿瘤的治疗提供创新且有效的途径。
Beyond Telomeres: Unveiling the Extratelomeric Functions of TERT in B-Cell Malignancies
肿瘤(癌症)患者之家