biostudies-literatureMangosh TLNational Cancer InstituteNCI NIH HHSNational Institute of General Medical SciencesNIH HHSNIGMS NIH HHS1235-1251https://www.ebi.ac.uk/biostudies/studies/S-EPMC8460604biostudies-literatureUnknown81(15)<h4>Background</h4>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-The ProstateSLX4IP N-terminus dictates telomeric localization in ALT-like castration-resistant prostate cancer cell lines.PMC8460604S10 OD016164R01 GM133841R01 CA240993Grabowska MMMangosh TLTaylor DJfalseSLX4IP N-terminus dictates telomeric localization in ALT-like castration-resistant prostate cancer cell lines.<h4>Background</h4>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-2021-01-01T00:00:00Z2021 Nov2026-05-31T16:01:28.922Z2025-02-19T01:27:42.682ZS-EPMC84606043449213310.1002/pros.24225