{"entity": "publication", "iuid": "07df3ae2eec54b01a884b242c7030b75", "timestamp": "2026-09-01T08:31:53.997Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/07df3ae2eec54b01a884b242c7030b75.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/07df3ae2eec54b01a884b242c7030b75"}}, "title": "Blocking Fra-1 sensitizes triple-negative breast cancer to PARP inhibitor.", "authors": [{"family": "Song", "given": "Dandan", "initials": "D"}, {"family": "He", "given": "Huan", "initials": "H"}, {"family": "Sinha", "given": "Indranil", "initials": "I"}, {"family": "Hases", "given": "Linnea", "initials": "L"}, {"family": "Yan", "given": "Feifei", "initials": "F"}, {"family": "Archer", "given": "Amena", "initials": "A"}, {"family": "Haldosen", "given": "Lars-Arne", "initials": "LA"}, {"family": "Zhao", "given": "Chunyan", "initials": "C"}, {"family": "Williams", "given": "Cecilia", "initials": "C"}], "type": "journal article", "published": "2021-05-28", "journal": {"title": "Cancer Lett.", "issn": "1872-7980", "volume": "506", "pages": "23-34", "issn-l": "0304-3835"}, "abstract": "The AP-1 member Fra-1 is overexpressed in TNBC and plays crucial roles in tumor progression and treatment resistance. In a previous large-scale screen, we identified PARP1 to be among 118 proteins that interact with endogenous chromatin-bound Fra-1 in TNBC cells. PARP1 inhibitor (olaparib) is currently in clinical use for treatment of BRCA-mutated TNBC breast cancer. Here, we demonstrate that the Fra-1-PARP1 interaction impacts the efficacy of olaparib treatment. We show that PARP1 interacts with and downregulates Fra-1, thereby reducing AP-1 transcriptional activity. Olaparib treatment, or silencing of PARP1, consequently, increases Fra-1 levels and enhances its transcriptional activity. Increased Fra-1 can have adverse effect, including treatment resistance. We also found that a large fraction of PARP1-regulated genes was dependent on Fra-1. We show that by inhibiting Fra-1/AP-1, non-BRCA-mutated TNBC cells can become sensitized to olaparib treatment. We identify that high PARP1 expression is indicative of a poor clinical outcome in breast cancer patients overall (P = 0.01), but not for HER-2 positive patients. In conclusion, by exploring the functionality of the Fra-1 and PARP1 interaction, we propose that targeting Fra-1 could serve as a combinatory therapeutic approach to improve olaparib treatment outcome for TNBC patients.", "doi": "10.1016/j.canlet.2021.02.018", "pmid": "33652085", "labels": [], "xrefs": [{"db": "pii", "key": "S0304-3835(21)00092-6"}], "notes": [], "created": "2026-08-21T11:14:37.137Z", "modified": "2026-08-21T11:14:37.148Z"}