{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["15(4)"],"submitter":["Bopple K"],"funding":["Hope Fund for Cancer Research Postdoctoral Fellowship, The Azrieli Faculty Scholars program and the Rivkin Scientific Scholar Award.","Rising Tide Foundation, Robert Bosch Stiftung (Stuttgart, Germany) and the Berthold Leibinger Stiftung","Berthold Leibinger Stiftung","was supported by a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund","Robert Bosch Stiftung","Jane Coffin Childs Memorial Fund for Medical Research","Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) TRR 221/INF"],"pubmed_abstract":["High-grade serous ovarian cancer (HGSOC) represents the most common and lethal subtype of ovarian cancer. Despite initial response to platinum-based standard therapy, patients commonly suffer from relapse that likely originates from drug-tolerant persister (DTP) cells. We generated isogenic clones of treatment-naïve and cisplatin-tolerant persister HGSOC cells. In addition, single-cell RNA sequencing of barcoded cells was performed in a xenograft model with HGSOC cell lines after platinum-based therapy. Published single-cell RNA-sequencing data from neo-adjuvant and non-treated HGSOC patients and patient data from TCGA were analyzed. DTP-derived cells exhibited morphological alterations and upregulation of epithelial-mesenchymal transition (EMT) markers. An aggressive subpopulation of DTP-derived cells showed high expression of the stress marker ATF3. Knockdown of ATF3 enhanced the sensitivity of aggressive DTP-derived cells to cisplatin-induced cell death, implying a role for ATF3 stress response in promoting a drug tolerant persister cell state. Furthermore, single cell lineage tracing to detect transcriptional changes in a HGSOC cell line-derived xenograft relapse model showed that cells derived from relapsed solid tumors express increased levels of EMT and multiple endoplasmic reticulum (ER) stress markers, including ATF3. Single cell RNA sequencing of epithelial cells from four HGSOC patients also identified a small cell population resembling DTP cells in all samples. Moreover, analysis of TCGA data from 259 HGSOC patients revealed a significant progression-free survival advantage for patients with low expression of the ATF3-associated partial EMT genes. These findings suggest that increased ATF3 expression together with partial EMT promote the development of aggressive DTP, and thereby relapse in HGSOC patients."],"journal":["Cell death & disease"],"pagination":["290"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11043376"],"repository":["biostudies-literature"],"pubmed_title":["ATF3 characterizes aggressive drug-tolerant persister cells in HGSOC."],"pmcid":["PMC11043376"],"pubmed_authors":["Oren Y","Kopp HG","Weller S","Dong M","Bopple K","Kleih M","Gaißler A","Essmann F","Liang C","Aulitzky WE","Henry WS","Aylon Y","Thiel J","Zipperer D","Oren M"],"additional_accession":[]},"is_claimable":false,"name":"ATF3 characterizes aggressive drug-tolerant persister cells in HGSOC.","description":"High-grade serous ovarian cancer (HGSOC) represents the most common and lethal subtype of ovarian cancer. Despite initial response to platinum-based standard therapy, patients commonly suffer from relapse that likely originates from drug-tolerant persister (DTP) cells. We generated isogenic clones of treatment-naïve and cisplatin-tolerant persister HGSOC cells. In addition, single-cell RNA sequencing of barcoded cells was performed in a xenograft model with HGSOC cell lines after platinum-based therapy. Published single-cell RNA-sequencing data from neo-adjuvant and non-treated HGSOC patients and patient data from TCGA were analyzed. DTP-derived cells exhibited morphological alterations and upregulation of epithelial-mesenchymal transition (EMT) markers. An aggressive subpopulation of DTP-derived cells showed high expression of the stress marker ATF3. Knockdown of ATF3 enhanced the sensitivity of aggressive DTP-derived cells to cisplatin-induced cell death, implying a role for ATF3 stress response in promoting a drug tolerant persister cell state. Furthermore, single cell lineage tracing to detect transcriptional changes in a HGSOC cell line-derived xenograft relapse model showed that cells derived from relapsed solid tumors express increased levels of EMT and multiple endoplasmic reticulum (ER) stress markers, including ATF3. Single cell RNA sequencing of epithelial cells from four HGSOC patients also identified a small cell population resembling DTP cells in all samples. Moreover, analysis of TCGA data from 259 HGSOC patients revealed a significant progression-free survival advantage for patients with low expression of the ATF3-associated partial EMT genes. These findings suggest that increased ATF3 expression together with partial EMT promote the development of aggressive DTP, and thereby relapse in HGSOC patients.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-06-02T01:36:11.011Z","creation":"2026-04-13T03:11:50.392Z"},"accession":"S-EPMC11043376","cross_references":{"pubmed":["38658567"],"doi":["10.1038/s41419-024-06674-x"]}}