{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317900/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317900"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"ZDHHC8-mediated β-catenin palmitoylation promotes WNT signaling activation and drives cisplatin resistance in osteosarcoma","description":"Chemoresistance remains a major challenge in osteosarcoma therapy, severely limiting the efficacy of cisplatin-based chemotherapy. Here, we identify the palmitoyltransferase ZDHHC8 as a critical determinant of cisplatin resistance and uncover a lipid modification–dependent mechanism that stabilizes β-catenin and sustains WNT signaling. ZDHHC8 expression was markedly upregulated in chemoresistant osteosarcoma tissues, and its knockdown significantly enhanced cisplatin-induced apoptosis both in vitro and in vivo. Transcriptomic profiling and functional assays revealed that ZDHHC8 depletion suppressed WNT/β-catenin signaling and diminished cancer stem cell–like properties. Mechanistically, ZDHHC8 directly interacted with β-catenin and catalyzed its C381-specific palmitoylation, which prevented proteasomal degradation and maintained protein stability. Mutation of C381 abolished β-catenin palmitoylation, resulting in reduced WNT activity and impaired stemness maintenance. Conversely, ZDHHC8 overexpression stabilized β-catenin and conferred cisplatin resistance. Collectively, our findings reveal a previously unrecognized ZDHHC8–β-catenin palmitoylation axis that governs WNT pathway activation and osteosarcoma chemoresistance. Targeting ZDHHC8 or disrupting β-catenin palmitoylation offers a promising therapeutic strategy to overcome drug resistance and improve osteosarcoma outcomes.","dates":{"publication":"2026/07/01"},"accession":"GSE317900","cross_references":{"GSM":["GSM9481401","GSM9481402","GSM9481397","GSM9481398","GSM9481399","GSM9481400","GSM9481395","GSM9481396"],"GPL":["16791"],"GSE":["317900"],"taxon":["Homo sapiens"]}}