Hou Kailong, Yu Yuyang, Li Duda, Zhang Yanduo, Zhang Ke, Tong Jinkai, Yang Kunxian, Jia Shuting
Faculty of Life Science and Technology, Kunming University of Science and Technology, 727 Jing Ming Nan Road, Kunming 650500, China.
Laboratory of Molecular Genetics of Aging and Tumor, Medical School, Kunming University of Science and Technology, 727 Jing Ming Nan Road, Kunming 650500, China.
Cancers (Basel). 2022 Apr 27;14(9):2194. doi: 10.3390/cancers14092194.
Telomeres are DNA-protein complexes that protect eukaryotic chromosome ends from being erroneously repaired by the DNA damage repair system, and the length of telomeres indicates the replicative potential of the cell. Telomeres shorten during each division of the cell, resulting in telomeric damage and replicative senescence. Tumor cells tend to ensure cell proliferation potential and genomic stability by activating telomere maintenance mechanisms (TMMs) for telomere lengthening. The alternative lengthening of telomeres (ALT) pathway is the most frequently activated TMM in tumors of mesenchymal and neuroepithelial origin, and ALT also frequently occurs during experimental cellular immortalization of mesenchymal cells. ALT is a process that relies on homologous recombination (HR) to elongate telomeres. However, some processes in the ALT mechanism remain poorly understood. Here, we review the most recent understanding of ALT mechanisms and processes, which may help us to better understand how the ALT pathway is activated in cancer cells and determine the potential therapeutic targets in ALT pathway-stabilized tumors.
端粒是一种DNA-蛋白质复合物，可保护真核染色体末端不被DNA损伤修复系统错误修复，端粒的长度表明细胞的复制潜力。在细胞的每次分裂过程中端粒都会缩短，导致端粒损伤和复制性衰老。肿瘤细胞倾向于通过激活端粒维持机制（TMMs）来延长端粒，从而确保细胞增殖潜力和基因组稳定性。端粒的替代延长（ALT）途径是间充质和神经上皮起源肿瘤中最常激活的TMM，并且ALT在间充质细胞的实验性细胞永生化过程中也经常发生。ALT是一个依赖同源重组（HR）来延长端粒的过程。然而，ALT机制中的一些过程仍了解甚少。在此，我们综述了对ALT机制和过程的最新认识，这可能有助于我们更好地理解ALT途径在癌细胞中是如何被激活的，并确定ALT途径稳定的肿瘤中的潜在治疗靶点。
