Recent studies have found that somatic gene mutations and environmental tumor‑promoting factors are both indispensable for tumor formation. Telomeric repeat‑binding factor (TRF)2 is the core component of the telomere shelterin complex, which plays an important role in chromosome stability and the maintenance of normal cell physiological states. In recent years, TRF2 and its role in tumor formation have gradually become a research hot topic, which has promoted in‑depth discussions into tumorigenesis and treatment strategies, and has achieved promising results. Some cells bypass elimination, due to either aging, apoptosis via mutations or abnormal prolongation of the mitotic cycle, and enter the telomere crisis period, where large‑scale DNA reorganization occurs repeatedly, which manifests as the precancerous cell cycle. Finally, at the end of the crisis cycle, the mutation activates either the expression level of telomerase or activates the alternative lengthening of telomere mechanism to extend the local telomeres. Under the protection of TRF2, chromosomes are gradually stabilized, immortal cells are formed and the stagewise mutation‑driven transformation of normal cells to cancer cells is completed. In addition, TRF2 also shares the characteristics of environmental tumor‑promoting factors. It acts on multiple signal transduction pathway‑related proteins associated with cell proliferation, and affects peripheral angiogenesis, inhibits the immune recognition and killing ability of the microenvironment, and maintains the stemness characteristics of tumor cells. TRF2 levels are abnormally elevated by a variety of tumor control proteins, which are more conducive to the protection of telomeres and the survival of tumor cells. In brief, the various regulatory mechanisms which tumor cells rely on to survive are organically integrated around TRF2, forming a regulatory network, which is conducive to the optimization of the survival direction of heterogeneous tumor cells, and promotes their survival and adaptability. In terms of clinical application, TRF2 is expected to become a new type of cancer prognostic marker and a new tumor treatment target. Inhibition of TRF2 overexpression could effectively cut off the core network regulating tumor cell survival, reduce drug resistance, or bypass the mutation under the pressure of tumor treatment selection, which may represent a promising therapeutic strategy for the complete eradication of tumors in the clinical setting. Based on recent research, the aim of the present review was to systematically elaborate on the basic structure and functional characteristics of TRF2 and its role in tumor formation, and to analyze the findings indicating that TRF2 deficiency or overexpression could cause severe damage to telomere function and telomere shortening, and induce DNA damage response and chromosomal instability.

中文翻译：

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端粒蛋白 TRF2 的异常功能诱导细胞突变和环境肿瘤促进因子的影响（综述）。

最近的研究发现，体细胞基因突变和环境促癌因素对于肿瘤的形成都是必不可少的。端粒重复结合因子 (TRF)2 是端粒保护蛋白复合物的核心成分，在染色体稳定性和维持细胞正常生理状态方面发挥着重要作用。近年来，TRF2及其在肿瘤形成中的作用逐渐成为研究热点，推动了对肿瘤发生和治疗策略的深入探讨，并取得了可喜的成果。一些细胞由于衰老、突变导致的细胞凋亡或有丝分裂周期的异常延长而绕过消除，进入端粒危机期，在此期间重复发生大规模的 DNA 重组，这表现为癌前细胞周期。最后，在危机周期结束时，突变会激活端粒酶的表达水平或激活端粒的替代延长机制以延长局部端粒。在TRF2的保护下，染色体逐渐稳定，形成永生细胞，完成正常细胞向癌细胞的阶段性突变驱动转化。此外，TRF2还具有环境促癌因子的特征。它作用于多种与细胞增殖相关的信号转导通路相关蛋白，影响外周血管生成，抑制微环境的免疫识别和杀伤能力，维持肿瘤细胞的干性特性。TRF2 水平被多种肿瘤控制蛋白异常升高，更有利于端粒的保护和肿瘤细胞的存活。总之，肿瘤细胞赖以生存的各种调控机制围绕TRF2有机整合，形成调控网络，有利于异质肿瘤细胞生存方向的优化，促进其生存和适应性。在临床应用方面，TRF2有望成为一种新型的癌症预后标志物和新的肿瘤治疗靶点。抑制TRF2过表达可以有效切断调节肿瘤细胞存活的核心网络，降低耐药性，或绕过肿瘤治疗选择压力下的突变，这可能是临床彻底根除肿瘤的一种有前景的治疗策略。