To ensure replicative immortality in cancer, telomeres must be maintained through activation of telomere maintenance mechanisms (TMMs) that are dependent on telomerase or the alternative lengthening of telomeres (ALT) pathway. Although TMM pathways have traditionally been considered to be mutually exclusive, ALT hallmarks have been identified in cancers defined as being telomerase-positive, supporting TMM coexistence. In castration-resistant prostate cancer (CRPC), in vitro models were thought to be universally dependent on telomerase as the primary TMM; however, CRPC models with androgen receptor (AR) loss demonstrate ALT hallmarks with limited telomerase activity and require ALT-associated PML bodies (APBs) for sustained telomere maintenance. The TMM coexistence in AR-negative CRPC is reliant on the ALT regulator protein, SLX4IP.

中文翻译：

---

SLX4IP N 末端决定 ALT 样去势抵抗性前列腺癌细胞系中的端粒定位


为了确保癌症的复制永生性，必须通过激活端粒维持机制（TMM）来维持端粒，该机制依赖于端粒酶或替代性端粒延长（ALT）途径。尽管传统上认为 TMM 通路是相互排斥的，但在定义为端粒酶阳性的癌症中已发现 ALT 标志，支持 TMM 共存。在去势抵抗性前列腺癌 (CRPC) 中，体外模型被认为普遍依赖端粒酶作为主要 TMM；然而，雄激素受体 (AR) 缺失的 CRPC 模型显示 ALT 标志具有有限的端粒酶活性，并且需要 ALT 相关的 PML 小体 (APB) 来持续维持端粒。 AR 阴性 CRPC 中 TMM 的共存依赖于 ALT 调节蛋白 SLX4IP。