{"entity": "researcher", "timestamp": "2026-06-02T11:20:36.757Z", "family": "Bai", "given": "Yu", "initials": "Y", "orcid": "0009-0002-0812-8917", "affiliations": ["Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/a1f57827cead428f8a7d7e4386eca3a3.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/a1f57827cead428f8a7d7e4386eca3a3"}}, "publications": [{"entity": "publication", "iuid": "1f47f9fb4e1e4013a73952ad427c61e2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1f47f9fb4e1e4013a73952ad427c61e2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1f47f9fb4e1e4013a73952ad427c61e2"}}, "title": "TGF\u03b2 signaling promotes cell cycle progression and resistance to the CDK4/6 inhibitor palbociclib through SOX4 transcriptional modulation in breast cancer cells.", "authors": [{"family": "Ali", "given": "Mohamad Moustafa", "initials": "MM", "orcid": "0000-0002-4902-0550", "researcher": {"href": "https://publications.scilifelab.se/researcher/780c944670ff4d7489410895569ac257.json"}}, {"family": "Itoh", "given": "Yuka", "initials": "Y"}, {"family": "Badji", "given": "Aisha Mariama Pereira", "initials": "AMP"}, {"family": "Gallant", "given": "Sarah", "initials": "S", "orcid": "0009-0003-9742-4706", "researcher": {"href": "https://publications.scilifelab.se/researcher/666f2f479a3e4421b0aa834d49c0d724.json"}}, {"family": "Tsirigoti", "given": "Chrysoula", "initials": "C", "orcid": "0000-0001-6554-738X", "researcher": {"href": "https://publications.scilifelab.se/researcher/369717d5e92a4045b701964c37fd0aa8.json"}}, {"family": "Bai", "given": "Yu", "initials": "Y", "orcid": "0009-0002-0812-8917", "researcher": {"href": "https://publications.scilifelab.se/researcher/a1f57827cead428f8a7d7e4386eca3a3.json"}}, {"family": "Filipek-G\u00f3rniok", "given": "Beata", "initials": "B"}, {"family": "Miyazawa", "given": "Keiji", "initials": "K", "orcid": "0000-0002-7835-7718", "researcher": {"href": "https://publications.scilifelab.se/researcher/71984836d37c463eaf5ded53bed887dc.json"}}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH", "orcid": "0000-0002-9508-896X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f705f7c509904a1db721ace2267ca48f.json"}}, {"family": "Moustakas", "given": "Aristidis", "initials": "A", "orcid": "0000-0001-9131-3827", "researcher": {"href": "https://publications.scilifelab.se/researcher/6c1626d991f3485e81232db174537e6d.json"}}], "type": "journal article", "published": "2026-02-04", "journal": {"title": "Cell Death Dis", "issn": "2041-4889", "volume": "17", "issue": "1", "pages": "209", "issn-l": "2041-4889"}, "abstract": "Cancer signaling encompasses a wide array of entangled molecular cascades that promote oncogenic progression and counteract the effect of tumor suppressors. Transforming growth factor \u03b2 (TGF\u03b2) induces complex and stage-dependent effects throughout tumor progression. During pre-malignant hyperplastic growth, TGF\u03b2 restricts cell proliferation and inflammation, while on the other hand, TGF\u03b2 promotes migration and distal metastasis of cancer cells. To dissect the temporal chromatin-based transcriptional response to TGF\u03b2, we employed 3D culture models of isogenic human breast epithelial cells, exemplified by non-oncogenic MCF-10A (MI) and their HRAS-transformed counterpart (MII). Genome-wide chromatin accessibility profiling revealed an extensive chromatin opening induced by TGF\u03b2 at transcription start sites and enhancer elements in both models, with a marked enrichment of SOX4 binding motifs in oncogenic cells. Transcriptomic analyses unexpectedly revealed the upregulation of DNA replication and DNA damage response pathways, following TGF\u03b2 stimulation of oncogenic MII 3D cultures. Canonical TGF\u03b2-driven programs, including epithelial-mesenchymal transition and metabolic reprogramming, were activated in both models. Notably, single-cell RNA-seq of primary breast tumors confirmed co-expression of SOX4 and cell cycle regulators. Mechanistically, we show that TGF\u03b2 induces the interaction between the MH2 domain of SMAD3 and the intrinsically disordered regions of SOX4, co-activating downstream gene targets. Validating the genome-wide analyses, we found that resistance of breast cancer cells to the CDK4/6 inhibitor palbociclib conferred by TGF\u03b2 stimulation was functionally dependent on SOX4. Collectively, our findings reveal an apparent oncogenic function of TGF\u03b2 in promoting cell cycle progression and drug resistance through SOX4, highlighting the pro-tumorigenic role of TGF\u03b2 signaling in breast cancer progression.", "doi": "10.1038/s41419-026-08435-4", "pmid": "41639049", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Short read": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12895049"}, {"db": "pii", "key": "10.1038/s41419-026-08435-4"}], "notes": [], "created": "2026-06-01T08:42:55.172Z", "modified": "2026-06-01T08:42:55.598Z"}]}