{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:11:33Z","timestamp":1792156293207,"version":"4.4.0"},"reference-count":110,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    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\n                    <jats:italic>SOX4<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1038\/s41419-026-08435-4","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T10:38:28Z","timestamp":1770201508000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["TGF\u03b2 signaling promotes cell cycle progression and resistance to the CDK4\/6 inhibitor palbociclib through SOX4 transcriptional modulation in breast cancer cells"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4902-0550","authenticated-orcid":false,"given":"Mohamad Moustafa","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha Mariama Pereira","family":"Badji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9742-4706","authenticated-orcid":false,"given":"Sarah","family":"Gallant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6554-738X","authenticated-orcid":false,"given":"Chrysoula","family":"Tsirigoti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0812-8917","authenticated-orcid":false,"given":"Yu","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Filipek-G\u00f3rniok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7835-7718","authenticated-orcid":false,"given":"Keiji","family":"Miyazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9508-896X","authenticated-orcid":false,"given":"Carl-Henrik","family":"Heldin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9131-3827","authenticated-orcid":false,"given":"Aristidis","family":"Moustakas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"8435_CR1","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1073\/pnas.82.1.119","volume":"82","author":"AB Roberts","year":"1985","unstructured":"Roberts AB, Anzano MA, Wakefield LM, Roche NS, Stern DF, Sporn MB. Type \u03b2 transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci USA. 1985;82:119\u201323.","journal-title":"Proc Natl Acad Sci USA"},{"key":"8435_CR2","doi-asserted-by":"crossref","unstructured":"Zhang Y, Alexander PB, Wang XF. TGF-\u03b2 family signaling in the control of cell proliferation and survival. Cold Spring Harb Perspect Biol. 2017;9.","DOI":"10.1101\/cshperspect.a022145"},{"key":"8435_CR3","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/S0092-8674(00)80127-0","volume":"86","author":"W Cui","year":"1996","unstructured":"Cui W, Fowlis DJ, Bryson S, Duffie E, Ireland H, Balmain A, et al. TGF\u03b21 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell. 1996;86:531\u201342.","journal-title":"Cell"},{"key":"8435_CR4","doi-asserted-by":"publisher","first-page":"8430","DOI":"10.1073\/pnas.0932636100","volume":"100","author":"PM Siegel","year":"2003","unstructured":"Siegel PM, Shu W, Cardiff RD, Muller WJ, Massagu\u00e9 J. Transforming growth factor \u03b2 signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. Proc Natl Acad Sci USA. 2003;100:8430\u20135.","journal-title":"Proc Natl Acad Sci USA"},{"key":"8435_CR5","doi-asserted-by":"publisher","first-page":"15231","DOI":"10.1073\/pnas.0406771101","volume":"101","author":"JM Scandura","year":"2004","unstructured":"Scandura JM, Boccuni P, Massagu\u00e9 J, Nimer SD. Transforming growth factor \u03b2-induced cell cycle arrest of human hematopoietic cells requires p57KIP2 up-regulation. Proc Natl Acad Sci USA. 2004;101:15231\u20136.","journal-title":"Proc Natl Acad Sci USA"},{"key":"8435_CR6","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1073\/pnas.98.3.992","volume":"98","author":"CR Chen","year":"2001","unstructured":"Chen CR, Kang Y, Massagu\u00e9 J. Defective repression of c-myc in breast cancer cells: a loss at the core of the transforming growth factor \u03b2 growth arrest program. Proc Natl Acad Sci USA. 2001;98:992\u20139.","journal-title":"Proc Natl Acad Sci USA"},{"key":"8435_CR7","doi-asserted-by":"crossref","unstructured":"Heldin C-H, Moustakas A. Signaling receptors for TGF-\u03b2 family members. Cold Spring Harb Perspect Biol. 2016;8.","DOI":"10.1101\/cshperspect.a022053"},{"key":"8435_CR8","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1101\/gad.330837.119","volume":"33","author":"E Aragon","year":"2019","unstructured":"Aragon E, Wang Q, Zou Y, Morgani SM, Ruiz L, Kaczmarska Z, et al. Structural basis for distinct roles of SMAD2 and SMAD3 in FOXH1 pioneer-directed TGF-\u03b2 signaling. Genes Dev. 2019;33:1506\u201324.","journal-title":"Genes Dev"},{"key":"8435_CR9","doi-asserted-by":"crossref","unstructured":"Morikawa M, Derynck R, Miyazono K. TGF-\u03b2 and the TGF-\u03b2 family: context-dependent roles in cell and tissue physiology. Cold Spring Harb Perspect Biol. 2016;8:a021873.","DOI":"10.1101\/cshperspect.a021873"},{"key":"8435_CR10","doi-asserted-by":"crossref","unstructured":"Zhang YE. Non-Smad signaling pathways of the TGF-\u03b2 family. Cold Spring Harb Perspect Biol. 2017;9:a022129.","DOI":"10.1101\/cshperspect.a022129"},{"key":"8435_CR11","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1007\/s00292-021-00934-9","volume":"42","author":"A Lebeau","year":"2021","unstructured":"Lebeau A, Denkert C. Updated WHO classification of tumors of the breast: the most important changes. Pathologe. 2021;42:270\u201380.","journal-title":"Pathologe"},{"key":"8435_CR12","doi-asserted-by":"publisher","first-page":"594","DOI":"10.6004\/jnccn.2023.0031","volume":"21","author":"WJ Gradishar","year":"2023","unstructured":"Gradishar WJ, Moran MS, Abraham J, Abramson V, Aft R, Agnese D, et al. NCCN Guidelines(R) insights: breast cancer, Version 4.2023. J Natl Compr Canc Netw. 2023;21:594\u2013608.","journal-title":"J Natl Compr Canc Netw"},{"key":"8435_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-024-00684-w","volume":"10","author":"E Noguchi","year":"2024","unstructured":"Noguchi E, Yamanaka T, Mukai H, Yamamoto N, Chung CF, Lu YS, et al. A phase 3 study (PATHWAY) of palbociclib plus tamoxifen in patients with HR-positive\/HER2-negative advanced breast cancer. NPJ Breast Cancer. 2024;10:76.","journal-title":"NPJ Breast Cancer"},{"key":"8435_CR14","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1016\/S1470-2045(21)00288-6","volume":"22","author":"Early Breast Cancer Trialists\u2019 Collaborative g.","year":"2021","unstructured":"Early Breast Cancer Trialists\u2019 Collaborative g. Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13,864 women in seven randomised trials. Lancet Oncol. 2021;22:1139\u201350.","journal-title":"Lancet Oncol"},{"key":"8435_CR15","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/s41591-024-03415-7","volume":"31","author":"F Cardoso","year":"2025","unstructured":"Cardoso F, O\u2019Shaughnessy J, Liu Z, McArthur H, Schmid P, Cortes J, et al. Pembrolizumab and chemotherapy in high-risk, early-stage, ER+\/HER2\u2212 breast cancer: a randomized phase 3 trial. Nat Med. 2025;31:442\u20138.","journal-title":"Nat Med"},{"key":"8435_CR16","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1159\/000508675","volume":"15","author":"AD Hartkopf","year":"2020","unstructured":"Hartkopf AD, Grischke EM, Brucker SY. Endocrine-resistant breast cancer: mechanisms and treatment. Breast Care. 2020;15:347\u201354.","journal-title":"Breast Care"},{"key":"8435_CR17","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1172\/JCI65416","volume":"123","author":"NE Bhola","year":"2013","unstructured":"Bhola NE, Balko JM, Dugger TC, Kuba MG, Sanchez V, Sanders M, et al. TGF-\u03b2 inhibition enhances chemotherapy action against triple-negative breast cancer. J Clin Investig. 2013;123:1348\u201358.","journal-title":"J Clin Investig"},{"key":"8435_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.semcancer.2023.10.004","volume":"97","author":"X Wang","year":"2023","unstructured":"Wang X, Eichhorn PJA, Thiery JP. TGF-\u03b2, EMT, and resistance to anti-cancer treatment. Semin Cancer Biol. 2023;97:1\u201311.","journal-title":"Semin Cancer Biol"},{"key":"8435_CR19","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cytogfr.2025.05.004","volume":"85","author":"W Luo","year":"2025","unstructured":"Luo W, Shi Q, Han M, Zhang Z, Reiter RJ, Ashrafizadeh M, et al. TGF-\u03b2-driven EMT in cancer progression and drug resistance. Cytokine Growth Factor Rev. 2025;85:11\u201325.","journal-title":"Cytokine Growth Factor Rev"},{"key":"8435_CR20","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/cr.2008.316","volume":"19","author":"D Padua","year":"2009","unstructured":"Padua D, Massagu\u00e9 J. Roles of TGFb in metastasis. Cell Res. 2009;19:89\u2013102.","journal-title":"Cell Res"},{"key":"8435_CR21","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/nrclinonc.2017.44","volume":"14","author":"T Shibue","year":"2017","unstructured":"Shibue T, Weinberg RA. EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat Rev Clin Oncol. 2017;14:611\u201329.","journal-title":"Nat Rev Clin Oncol"},{"key":"8435_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2039","volume":"3","author":"A Bruna","year":"2012","unstructured":"Bruna A, Greenwood W, Le Quesne J, Teschendorff A, Miranda-Saavedra D, Rueda OM, et al. TGF\u03b2 induces the formation of tumour-initiating cells in claudin-low breast cancer. Nat Commun. 2012;3:1055.","journal-title":"Nat Commun"},{"key":"8435_CR23","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/bjc.2016.255","volume":"115","author":"C Bellomo","year":"2016","unstructured":"Bellomo C, Caja L, Moustakas A. Transforming growth factor \u03b2 as regulator of cancer stemness and metastasis. Br J Cancer. 2016;115:761\u20139.","journal-title":"Br J Cancer"},{"key":"8435_CR24","doi-asserted-by":"publisher","first-page":"2462","DOI":"10.1101\/gad.10.19.2462","volume":"10","author":"M Oft","year":"1996","unstructured":"Oft M, Peli J, Rudaz C, Schwarz H, Beug H, Reichmann E. TGF-\u03b21 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev. 1996;10:2462\u201377.","journal-title":"Genes Dev"},{"key":"8435_CR25","doi-asserted-by":"publisher","first-page":"6182","DOI":"10.1016\/j.cell.2024.08.014","volume":"187","author":"JH Lee","year":"2024","unstructured":"Lee JH, Sanchez-Rivera FJ, He L, Basnet H, Chen FX, Spina E, et al. TGF-\u03b2 and RAS jointly unmask primed enhancers to drive metastasis. Cell. 2024;187:6182\u201399 e29.","journal-title":"Cell"},{"key":"8435_CR26","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1016\/j.ymthe.2020.05.026","volume":"28","author":"Y Qiao","year":"2020","unstructured":"Qiao Y, Wang Z, Tan F, Chen J, Lin J, Yang J, et al. Enhancer reprogramming within pre-existing topologically associated domains promotes TGF-\u03b2-induced EMT and cancer metastasis. Mol Ther. 2020;28:2083\u201395.","journal-title":"Mol Ther"},{"key":"8435_CR27","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1038\/sj.onc.1210741","volume":"27","author":"A Gal","year":"2008","unstructured":"Gal A, Sjoblom T, Fedorova L, Imreh S, Beug H, Moustakas A. Sustained TGF \u03b2 exposure suppresses Smad and non-Smad signalling in mammary epithelial cells, leading to EMT and inhibition of growth arrest and apoptosis. Oncogene. 2008;27:1218\u201330.","journal-title":"Oncogene"},{"key":"8435_CR28","doi-asserted-by":"crossref","unstructured":"Katsuno Y, Meyer DS, Zhang Z, Shokat KM, Akhurst RJ, Miyazono K, et al. Chronic TGF-\u03b2 exposure drives stabilized EMT, tumor stemness, and cancer drug resistance with vulnerability to bitopic mTOR inhibition. Sci Signal. 2019;12.","DOI":"10.1126\/scisignal.aau8544"},{"key":"8435_CR29","doi-asserted-by":"publisher","first-page":"2509","DOI":"10.1038\/s41388-021-01711-x","volume":"40","author":"M Jalalirad","year":"2021","unstructured":"Jalalirad M, Haddad TC, Salisbury JL, Radisky D, Zhang M, Schroeder M, et al. Aurora-A kinase oncogenic signaling mediates TGF-\u03b2-induced triple-negative breast cancer plasticity and chemoresistance. Oncogene. 2021;40:2509\u201323.","journal-title":"Oncogene"},{"key":"8435_CR30","doi-asserted-by":"publisher","first-page":"2138","DOI":"10.1158\/1535-7163.MCT-12-0562","volume":"11","author":"F Liu","year":"2012","unstructured":"Liu F, Korc M. Cdk4\/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012;11:2138\u201348.","journal-title":"Mol Cancer Ther"},{"key":"8435_CR31","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1080\/15384101.2021.1909261","volume":"20","author":"SE Nataraj","year":"2021","unstructured":"Nataraj SE, Blain SW. A cyclin D-CDK6 dimer helps to reshuffle cyclin-dependent kinase inhibitors (CKI) to overcome TGF-\u03b2-mediated arrest and maintain CDK2 activity. Cell Cycle. 2021;20:808\u201318.","journal-title":"Cell Cycle"},{"key":"8435_CR32","doi-asserted-by":"publisher","first-page":"2667","DOI":"10.1016\/j.celrep.2019.02.023","volume":"26","author":"L Cornell","year":"2019","unstructured":"Cornell L, Wander SA, Visal T, Wagle N, Shapiro GI. MicroRNA-mediated suppression of the TGF-\u03b2 pathway confers transmissible and reversible CDK4\/6 inhibitor resistance. Cell Rep. 2019;26:2667\u201380.e7.","journal-title":"Cell Rep"},{"key":"8435_CR33","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02029-4","volume":"23","author":"S Poulet","year":"2024","unstructured":"Poulet S, Dai M, Wang N, Yan G, Boudreault J, Daliah G, et al. Genome-wide in vivo CRISPR screen identifies TGF\u03b23 as actionable biomarker of palbociclib resistance in triple-negative breast cancer. Mol Cancer. 2024;23:118.","journal-title":"Mol Cancer"},{"key":"8435_CR34","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01794-5","volume":"22","author":"E Vasilaki","year":"2024","unstructured":"Vasilaki E, Bai Y, Ali MM, Sundqvist A, Moustakas A, Heldin C-H. \u0394Np63 bookmarks and creates an accessible epigenetic environment for TGF\u03b2-induced cancer cell stemness and invasiveness. Cell Commun Signal. 2024;22:411.","journal-title":"Cell Commun Signal"},{"key":"8435_CR35","doi-asserted-by":"publisher","first-page":"2330","DOI":"10.1002\/1878-0261.13215","volume":"16","author":"Y Tsubakihara","year":"2022","unstructured":"Tsubakihara Y, Ohata Y, Okita Y, Younis S, Eriksson J, Sellin ME, et al. TGF\u03b2 selects for pro-stemness over pro-invasive phenotypes during cancer cell epithelial-mesenchymal transition. Mol Oncol. 2022;16:2330\u201354.","journal-title":"Mol Oncol"},{"key":"8435_CR36","doi-asserted-by":"crossref","unstructured":"Fu H, Itoh Y, Sawaguchi T, Otake S, Omata C, Saitoh M, et al. Identification of a distal enhancer that regulates TGF-\u03b2-induced SNAI1 expression. Cancer Sci. 2025:2137\u201349.","DOI":"10.1111\/cas.70091"},{"key":"8435_CR37","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202400978R","volume":"38","author":"Y Itoh","year":"2024","unstructured":"Itoh Y, Miyake K, Koinuma D, Omata C, Saitoh M, Miyazawa K. Analysis of the DNA-binding properties of TGF-\u03b2-activated Smad complexes unveils a possible molecular basis for cellular context-dependent signaling. FASEB J. 2024;38:e23877.","journal-title":"FASEB J"},{"key":"8435_CR38","doi-asserted-by":"publisher","first-page":"W739","DOI":"10.1093\/nar\/gkac382","volume":"50","author":"A Ianevski","year":"2022","unstructured":"Ianevski A, Giri AK, Aittokallio T. SynergyFinder 3.0: an interactive analysis and consensus interpretation of multi-drug synergies across multiple samples. Nucleic Acids Res. 2022;50:W739\u2013W43.","journal-title":"Nucleic Acids Res"},{"key":"8435_CR39","doi-asserted-by":"crossref","unstructured":"Panara V, Yu H, Peng D, Staxang K, Hodik M, Filipek-Gorniok B, et al. Multiple cis-regulatory elements control prox1a expression in distinct lymphatic vascular beds. Development. 2024;151:dev202525.","DOI":"10.1242\/dev.202525"},{"key":"8435_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05280-z","volume":"13","author":"C Tsirigoti","year":"2022","unstructured":"Tsirigoti C, Ali MM, Maturi V, Heldin CH, Moustakas A. Loss of SNAI1 induces cellular plasticity in invasive triple-negative breast cancer cells. Cell Death Dis. 2022;13:832.","journal-title":"Cell Death Dis"},{"key":"8435_CR41","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15\u201321.","journal-title":"Bioinformatics"},{"key":"8435_CR42","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","volume":"30","author":"Y Liao","year":"2014","unstructured":"Liao Y, Smyth GK, Shi W. featureCounts: an efficient general-purpose program for assigning sequence reads to genomic features. Bioinformatics. 2014;30:923\u201330.","journal-title":"Bioinformatics"},{"key":"8435_CR43","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.","journal-title":"Genome Biol"},{"key":"8435_CR44","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","volume":"1","author":"A Liberzon","year":"2015","unstructured":"Liberzon A, Birger C, Thorvaldsdottir H, Ghandi M, Mesirov JP, Tamayo P. The Molecular Signatures Database (MSigDB) Hallmark Gene Set Collection. Cell Syst. 2015;1:417\u201325.","journal-title":"Cell Syst"},{"key":"8435_CR45","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","volume":"42","author":"Y Hao","year":"2024","unstructured":"Hao Y, Stuart T, Kowalski MH, Choudhary S, Hoffman P, Hartman A, et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat Biotechnol. 2024;42:293\u2013304.","journal-title":"Nat Biotechnol"},{"key":"8435_CR46","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.cels.2019.03.003","volume":"8","author":"CS McGinnis","year":"2019","unstructured":"McGinnis CS, Murrow LM, Gartner ZJ. DoubletFindEr: doublet detection in single-cell RNA sequencing data using artificial nearest neighbors. Cell Syst. 2019;8:329\u201337.e4.","journal-title":"Cell Syst"},{"key":"8435_CR47","doi-asserted-by":"publisher","first-page":"21 9","DOI":"10.1002\/0471142727.mb2129s109","volume":"109","author":"JD Buenrostro","year":"2015","unstructured":"Buenrostro JD, Wu B, Chang HY, Greenleaf WJ. ATAC-seq: a method for assaying chromatin accessibility genome-wide. Curr Protoc Mol Biol. 2015;109:21 9\u20139 9.","journal-title":"Curr Protoc Mol Biol"},{"key":"8435_CR48","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","volume":"26","author":"AR Quinlan","year":"2010","unstructured":"Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010;26:841\u20132.","journal-title":"Bioinformatics"},{"key":"8435_CR49","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","volume":"38","author":"S Heinz","year":"2010","unstructured":"Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38:576\u201389.","journal-title":"Mol Cell"},{"key":"8435_CR50","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1002\/jcp.30975","volume":"238","author":"K Tzavlaki","year":"2023","unstructured":"Tzavlaki K, Ohata Y, Mor\u00e9n A, Watanabe Y, Eriksson J, Tsuchiya M, et al. The liver kinase B1 supports mammary epithelial morphogenesis by inhibiting critical factors that mediate epithelial-mesenchymal transition. J Cell Physiol. 2023;238:790\u2013812.","journal-title":"J Cell Physiol"},{"key":"8435_CR51","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1023\/A:1006461422273","volume":"65","author":"SJ Santner","year":"2001","unstructured":"Santner SJ, Dawson PJ, Tait L, Soule HD, Eliason J, Mohamed AN, et al. Malignant MCF10CA1 cell lines derived from premalignant human breast epithelial MCF10AT cells. Breast Cancer Res Treat. 2001;65:101\u201310.","journal-title":"Breast Cancer Res Treat"},{"key":"8435_CR52","unstructured":"Corces MR, Granja JM, Shams S, Louie BH, Seoane JA, Zhou W, et al. The chromatin accessibility landscape of primary human cancers. Science. 2018;362."},{"key":"8435_CR53","doi-asserted-by":"publisher","first-page":"e2004986","DOI":"10.1371\/journal.pbio.2004986","volume":"16","author":"EM Michalak","year":"2018","unstructured":"Michalak EM, Milevskiy MJG, Joyce RM, Dekkers JF, Jamieson PR, Pal B, et al. Canonical PRC2 function is essential for mammary gland development and affects chromatin compaction in mammary organoids. PLoS Biol. 2018;16:e2004986.","journal-title":"PLoS Biol"},{"key":"8435_CR54","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/nature12787","volume":"507","author":"R Andersson","year":"2014","unstructured":"Andersson R, Gebhard C, Miguel-Escalada I, Hoof I, Bornholdt J, Boyd M, et al. An atlas of active enhancers across human cell types and tissues. Nature. 2014;507:455\u201361.","journal-title":"Nature"},{"key":"8435_CR55","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1126\/science.aau0320","volume":"361","author":"EEM Furlong","year":"2018","unstructured":"Furlong EEM, Levine M. Developmental enhancers and chromosome topology. Science. 2018;361:1341\u20135.","journal-title":"Science"},{"key":"8435_CR56","doi-asserted-by":"publisher","first-page":"9578","DOI":"10.1093\/nar\/gky755","volume":"46","author":"SJ Vervoort","year":"2018","unstructured":"Vervoort SJ, Lourenco AR, Tufegdzic Vidakovic A, Mocholi E, Sandoval JL, Rueda OM, et al. SOX4 can redirect TGF-\u03b2-mediated SMAD3-transcriptional output in a context-dependent manner to promote tumorigenesis. Nucleic Acids Res. 2018;46:9578\u201390.","journal-title":"Nucleic Acids Res"},{"key":"8435_CR57","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1053\/j.gastro.2020.07.047","volume":"159","author":"JY Yang","year":"2020","unstructured":"Yang JY, Jie Z, Mathews A, Zhou X, Li Y, Gu M, et al. Intestinal epithelial TBK1 prevents differentiation of T-helper 17 cells and tumorigenesis in mice. Gastroenterology. 2020;159:1793\u2013806.","journal-title":"Gastroenterology"},{"key":"8435_CR58","doi-asserted-by":"publisher","first-page":"7822","DOI":"10.1096\/fj.201801936RRR","volume":"33","author":"Y Zhang","year":"2019","unstructured":"Zhang Y, Unnithan RVM, Hamidi A, Caja L, Saupe F, Moustakas A, et al. TANK-binding kinase 1 is a mediator of platelet-induced EMT in mammary carcinoma cells. FASEB J. 2019;33:7822\u201332.","journal-title":"FASEB J"},{"key":"8435_CR59","doi-asserted-by":"publisher","first-page":"E7","DOI":"10.1371\/journal.pbio.0020007","volume":"2","author":"HY Chang","year":"2004","unstructured":"Chang HY, Sneddon JB, Alizadeh AA, Sood R, West RB, Montgomery K, et al. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol. 2004;2:E7.","journal-title":"PLoS Biol"},{"key":"8435_CR60","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.ccr.2006.09.006","volume":"10","author":"G Wei","year":"2006","unstructured":"Wei G, Twomey D, Lamb J, Schlis K, Agarwal J, Stam RW, et al. Gene expression-based chemical genomics identifies rapamycin as a modulator of MCL1 and glucocorticoid resistance. Cancer Cell. 2006;10:331\u201342.","journal-title":"Cancer Cell"},{"key":"8435_CR61","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/nature04296","volume":"439","author":"AH Bild","year":"2006","unstructured":"Bild AH, Yao G, Chang JT, Wang Q, Potti A, Chasse D, et al. Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature. 2006;439:353\u20137.","journal-title":"Nature"},{"key":"8435_CR62","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1612-0","volume":"20","author":"D Repana","year":"2019","unstructured":"Repana D, Nulsen J, Dressler L, Bortolomeazzi M, Venkata SK, Tourna A, et al. The Network of Cancer Genes (NCG): a comprehensive catalogue of known and candidate cancer genes from cancer sequencing screens. Genome Biol. 2019;20:1.","journal-title":"Genome Biol"},{"key":"8435_CR63","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1200\/JCO.2008.18.1370","volume":"27","author":"JS Parker","year":"2009","unstructured":"Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27:1160\u20137.","journal-title":"J Clin Oncol"},{"key":"8435_CR64","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1093\/bioinformatics\/btv693","volume":"32","author":"DM Gendoo","year":"2016","unstructured":"Gendoo DM, Ratanasirigulchai N, Schroder MS, Pare L, Parker JS, Prat A, et al. Genefu: an R\/Bioconductor package for computation of gene expression-based signatures in breast cancer. Bioinformatics. 2016;32:1097\u20139.","journal-title":"Bioinformatics"},{"key":"8435_CR65","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.7150\/thno.15083","volume":"6","author":"C Wang","year":"2016","unstructured":"Wang C, Jin H, Wang N, Fan S, Wang Y, Zhang Y, et al. Gas6\/Axl Axis contributes to chemoresistance and metastasis in breast cancer through Akt\/GSK-3\u03b2\/\u03b2-catenin signaling. Theranostics. 2016;6:1205\u201319.","journal-title":"Theranostics"},{"key":"8435_CR66","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1038\/s41588-021-00911-1","volume":"53","author":"SZ Wu","year":"2021","unstructured":"Wu SZ, Al-Eryani G, Roden DL, Junankar S, Harvey K, Andersson A, et al. A single-cell and spatially resolved atlas of human breast cancers. Nat Genet. 2021;53:1334\u201347.","journal-title":"Nat Genet"},{"key":"8435_CR67","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","volume":"630","author":"J Abramson","year":"2024","unstructured":"Abramson J, Adler J, Dunger J, Evans R, Green T, Pritzel A, et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature. 2024;630:493\u2013500.","journal-title":"Nature"},{"key":"8435_CR68","first-page":"20327","volume":"278","author":"J Chai","year":"2003","unstructured":"Chai J, Wu JW, Yan N, Massague J, Pavletich NP, Shi Y. Features of a Smad3 MH1-DNA complex. Roles of water and zinc in DNA binding. J Biol Chem. 2003;278:20327\u201331.","journal-title":"Roles of water and zinc in DNA binding. J Biol Chem"},{"key":"8435_CR69","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1042\/BJ20111768","volume":"443","author":"R Jauch","year":"2012","unstructured":"Jauch R, Ng CK, Narasimhan K, Kolatkar PR. The crystal structure of the Sox4 HMG domain-DNA complex suggests a mechanism for positional interdependence in DNA recognition. Biochem J. 2012;443:39\u201347.","journal-title":"Biochem J"},{"key":"8435_CR70","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.molcel.2020.05.032","volume":"79","author":"S Brodsky","year":"2020","unstructured":"Brodsky S, Jana T, Mittelman K, Chapal M, Kumar DK, Carmi M, et al. Intrinsically disordered regions direct transcription factor in vivo binding specificity. Mol Cell. 2020;79:459\u201371.e4.","journal-title":"Mol Cell"},{"key":"8435_CR71","doi-asserted-by":"crossref","unstructured":"Vervoort SJ, de Jong OG, Roukens MG, Frederiks CL, Vermeulen JF, Lourenco AR, et al. Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis. Elife. 2018;7.","DOI":"10.7554\/eLife.27706"},{"key":"8435_CR72","doi-asserted-by":"publisher","first-page":"D1242","DOI":"10.1093\/nar\/gkac911","volume":"51","author":"H Yingtaweesittikul","year":"2023","unstructured":"Yingtaweesittikul H, Wu J, Mongia A, Peres R, Ko K, Nagarajan N, et al. CREAMMIST: an integrative probabilistic database for cancer drug response prediction. Nucleic Acids Res. 2023;51:D1242\u2013D8.","journal-title":"Nucleic Acids Res"},{"key":"8435_CR73","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.3892\/ol.2011.375","volume":"2","author":"S Vranic","year":"2011","unstructured":"Vranic S, Gatalica Z, Wang ZY. Update on the molecular profile of the MDA-MB-453 cell line as a model for apocrine breast carcinoma studies. Oncol Lett. 2011;2:1131\u20137.","journal-title":"Oncol Lett"},{"key":"8435_CR74","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32828-6","volume":"13","author":"M Palafox","year":"2022","unstructured":"Palafox M, Monserrat L, Bellet M, Villacampa G, Gonzalez-Perez A, Oliveira M, et al. High p16 expression and heterozygous RB1 loss are biomarkers for CDK4\/6 inhibitor resistance in ER+ breast cancer. Nat Commun. 2022;13:5258.","journal-title":"Nat Commun"},{"key":"8435_CR75","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1007\/s10549-021-06127-5","volume":"186","author":"L Lanceta","year":"2021","unstructured":"Lanceta L, Lypova N, O\u2019Neill C, Li X, Rouchka E, Chesney J, et al. Differential gene expression analysis of palbociclib-resistant TNBC via RNA-seq. Breast Cancer Res Treat. 2021;186:677\u201386.","journal-title":"Breast Cancer Res Treat"},{"key":"8435_CR76","doi-asserted-by":"crossref","unstructured":"Karlsson M, Zhang C, Mear L, Zhong W, Digre A, Katona B, et al. A single-cell type transcriptomics map of human tissues. Sci Adv. 2021;7.","DOI":"10.1126\/sciadv.abh2169"},{"key":"8435_CR77","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1038\/s41592-020-0907-8","volume":"17","author":"A Sethi","year":"2020","unstructured":"Sethi A, Gu M, Gumusgoz E, Chan L, Yan KK, Rozowsky J, et al. Supervised enhancer prediction with epigenetic pattern recognition and targeted validation. Nat Methods. 2020;17:807\u201314.","journal-title":"Nat Methods"},{"key":"8435_CR78","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cell.2008.07.001","volume":"134","author":"J Massagu\u00e9","year":"2008","unstructured":"Massagu\u00e9 J. TGF\u03b2 in Cancer. Cell. 2008;134:215\u201330.","journal-title":"Cell"},{"key":"8435_CR79","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1016\/j.immuni.2019.03.024","volume":"50","author":"E Batll\u00e9","year":"2019","unstructured":"Batll\u00e9 E, Massagu\u00e9 J. Transforming Growth Factor-\u03b2 Signaling in Immunity and Cancer. Immunity. 2019;50:924\u201340.","journal-title":"Immunity"},{"key":"8435_CR80","doi-asserted-by":"crossref","unstructured":"Habanjar O, Diab-Assaf M, Caldefie-Chezet F, Delort L. 3D Cell culture systems: tumor application, advantages, and disadvantages. Int J Mol Sci. 2021;22:12200.","DOI":"10.3390\/ijms222212200"},{"key":"8435_CR81","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1080\/13816810500374441","volume":"26","author":"RK Koenekoop","year":"2005","unstructured":"Koenekoop RK. RPGRIP1 is mutated in Leber congenital amaurosis: a mini-review. Ophthalmic Genet. 2005;26:175\u20139.","journal-title":"Ophthalmic Genet"},{"key":"8435_CR82","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41439-019-0041-2","volume":"6","author":"M Altaraihi","year":"2019","unstructured":"Altaraihi M, Wadt K, Ek J, Gerdes AM, Ostergaard E. A healthy individual with a homozygous PTCH2 frameshift variant: are variants of PTCH2 associated with nevoid basal cell carcinoma syndrome?. Hum Genome Var. 2019;6:10.","journal-title":"Hum Genome Var"},{"key":"8435_CR83","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1084\/jem.20150556","volume":"213","author":"C Klein","year":"2016","unstructured":"Klein C, Zwick A, Kissel S, Forster CU, Pfeifer D, Follo M, et al. Ptch2 loss drives myeloproliferation and myeloproliferative neoplasm progression. J Exp Med. 2016;213:273\u201390.","journal-title":"J Exp Med"},{"key":"8435_CR84","doi-asserted-by":"publisher","first-page":"E3000","DOI":"10.1073\/pnas.1504671112","volume":"112","author":"P Shathasivam","year":"2015","unstructured":"Shathasivam P, Kollara A, Ringuette MJ, Virtanen C, Wrana JL, Brown TJ. Human ortholog of Drosophila melted impedes SMAD2 release from TGF-\u03b2 receptor I to inhibit TGF-\u03b2 signaling. Proc Natl Acad Sci USA. 2015;112:E3000\u20139.","journal-title":"Proc Natl Acad Sci USA"},{"key":"8435_CR85","doi-asserted-by":"publisher","first-page":"1985","DOI":"10.1101\/gr.249326.119","volume":"29","author":"RV Chereji","year":"2019","unstructured":"Chereji RV, Eriksson PR, Ocampo J, Prajapati HK, Clark DJ. Accessibility of promoter DNA is not the primary determinant of chromatin-mediated gene regulation. Genome Res. 2019;29:1985\u201395.","journal-title":"Genome Res"},{"key":"8435_CR86","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13072-019-0260-2","volume":"12","author":"RR Starks","year":"2019","unstructured":"Starks RR, Biswas A, Jain A, Tuteja G. Combined analysis of dissimilar promoter accessibility and gene expression profiles identifies tissue-specific genes and actively repressed networks. Epigenet Chromatin. 2019;12:16.","journal-title":"Epigenet Chromatin"},{"key":"8435_CR87","doi-asserted-by":"publisher","DOI":"10.15252\/msb.202210979","volume":"18","author":"K Kiani","year":"2022","unstructured":"Kiani K, Sanford EM, Goyal Y, Raj A. Changes in chromatin accessibility are not concordant with transcriptional changes for single-factor perturbations. Mol Syst Biol. 2022;18:e10979.","journal-title":"Mol Syst Biol"},{"key":"8435_CR88","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-60482-1","volume":"16","author":"D Hong","year":"2025","unstructured":"Hong D, Shu M, Liu J, Liu L, Cheng H, Zhu M, et al. Divergent combinations of enhancers encode spatial gene expression. Nat Commun. 2025;16:5091.","journal-title":"Nat Commun"},{"key":"8435_CR89","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04406-2","volume":"9","author":"Z Ji","year":"2018","unstructured":"Ji Z, He L, Rotem A, Janzer A, Cheng CS, Regev A, et al. Genome-scale identification of transcription factors that mediate an inflammatory network during breast cellular transformation. Nat Commun. 2018;9:2068.","journal-title":"Nat Commun"},{"key":"8435_CR90","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1158\/0008-5472.CAN-15-1868","volume":"76","author":"Bilir","year":"2016","unstructured":"Bilir, Osunkoya B, Wiles AO, WGt, Sannigrahi S, Lefebvre V, et al. SOX4 is essential for prostate tumorigenesis initiated by PTEN ablation. Cancer Res. 2016;76:1112\u201321.","journal-title":"Cancer Res"},{"key":"8435_CR91","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1038\/ng.2764","volume":"45","author":"N Cancer Genome Atlas Research","year":"2013","unstructured":"Cancer Genome Atlas Research N, Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet. 2013;45:1113\u201320.","journal-title":"Nat Genet"},{"key":"8435_CR92","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0680-1","volume":"16","author":"H Wang","year":"2017","unstructured":"Wang H, Huo X, Yang XR, He J, Cheng L, Wang N, et al. STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4. Mol Cancer. 2017;16:136.","journal-title":"Mol Cancer"},{"key":"8435_CR93","doi-asserted-by":"publisher","first-page":"41434","DOI":"10.1074\/jbc.M111.300863","volume":"286","author":"H Ikushima","year":"2011","unstructured":"Ikushima H, Todo T, Ino Y, Takahashi M, Saito N, Miyazawa K, et al. Glioma-initiating cells retain their tumorigenicity through integration of the Sox axis and Oct4 protein. J Biol Chem. 2011;286:41434\u201341.","journal-title":"J Biol Chem"},{"key":"8435_CR94","doi-asserted-by":"publisher","first-page":"6343","DOI":"10.1038\/s41388-021-02004-z","volume":"40","author":"MG Roukens","year":"2021","unstructured":"Roukens MG, Frederiks CL, Seinstra D, Braccioli L, Khalil AA, Pals C, et al. Regulation of a progenitor gene program by SOX4 is essential for mammary tumor proliferation. Oncogene. 2021;40:6343\u201353.","journal-title":"Oncogene"},{"key":"8435_CR95","doi-asserted-by":"publisher","first-page":"e53238","DOI":"10.1371\/journal.pone.0053238","volume":"8","author":"SJ Vervoort","year":"2013","unstructured":"Vervoort SJ, Lourenco AR, van Boxtel R, Coffer PJ. SOX4 mediates TGF-\u03b2-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition. PLoS One. 2013;8:e53238.","journal-title":"PLoS One"},{"key":"8435_CR96","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/jcp.2005.034389","volume":"60","author":"GC Santos","year":"2007","unstructured":"Santos GC, Zielenska M, Prasad M, Squire JA. Chromosome 6p amplification and cancer progression. J Clin Pathol. 2007;60:1\u20137.","journal-title":"J Clin Pathol"},{"key":"8435_CR97","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/j.annonc.2024.04.013","volume":"35","author":"MP Goetz","year":"2024","unstructured":"Goetz MP, Toi M, Huober J, Sohn J, Tredan O, Park IH, et al. Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3. Ann Oncol. 2024;35:718\u201327.","journal-title":"Ann Oncol"},{"key":"8435_CR98","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1038\/onc.2016.379","volume":"36","author":"C Yang","year":"2017","unstructured":"Yang C, Li Z, Bhatt T, Dickler M, Giri D, Scaltriti M, et al. Acquired CDK6 amplification promotes breast cancer resistance to CDK4\/6 inhibitors and loss of ER signaling and dependence. Oncogene. 2017;36:2255\u201364.","journal-title":"Oncogene"},{"key":"8435_CR99","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/j.ccell.2017.11.006","volume":"32","author":"X Gong","year":"2017","unstructured":"Gong X, Litchfield LM, Webster Y, Chio LC, Wong SS, Stewart TR, et al. Genomic aberrations that activate D-type cyclins are associated with enhanced sensitivity to the CDK4 and CDK6 inhibitor abemaciclib. Cancer Cell. 2017;32:761\u201376.e6.","journal-title":"Cancer Cell"},{"key":"8435_CR100","doi-asserted-by":"publisher","first-page":"2301","DOI":"10.1158\/0008-5472.CAN-15-0728","volume":"76","author":"MT Herrera-Abreu","year":"2016","unstructured":"Herrera-Abreu MT, Palafox M, Asghar U, Rivas MA, Cutts RJ, Garcia-Murillas I, et al. Early adaptation and acquired resistance to CDK4\/6 inhibition in estrogen receptor-positive breast cancer. Cancer Res. 2016;76:2301\u201313.","journal-title":"Cancer Res"},{"key":"8435_CR101","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-02980-2","volume":"11","author":"W Ji","year":"2020","unstructured":"Ji W, Zhang W, Wang X, Shi Y, Yang F, Xie H, et al. c-myc regulates the sensitivity of breast cancer cells to palbociclib via c-myc\/miR-29b-3p\/CDK6 axis. Cell Death Dis. 2020;11:760.","journal-title":"Cell Death Dis"},{"key":"8435_CR102","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1158\/2159-8290.CD-19-1390","volume":"10","author":"SA Wander","year":"2020","unstructured":"Wander SA, Cohen O, Gong X, Johnson GN, Buendia-Buendia JE, Lloyd MR, et al. The genomic landscape of intrinsic and acquired resistance to cyclin-dependent kinase 4\/6 inhibitors in patients with hormone receptor-positive metastatic breast cancer. Cancer Discov. 2020;10:1174\u201393.","journal-title":"Cancer Discov"},{"key":"8435_CR103","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-025-01041-1","volume":"9","author":"NM Kettner","year":"2025","unstructured":"Kettner NM, Bui TN, Navarro-Yepes J, Ghotbaldini S, Quintela B, Luo CK, et al. IL-6 predicts CDK4\/6 inhibitor resistance, identifying STAT3 as a target in HR+\/HER2-negative metastatic breast cancer. NPJ Precis Oncol. 2025;9:260.","journal-title":"NPJ Precis Oncol"},{"key":"8435_CR104","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41420-025-02336-9","volume":"11","author":"C Chen","year":"2025","unstructured":"Chen C, Chen Z, Zhao J, Wen X, Yao H, Weng Z, et al. TMEM45A enhances palbociclib resistance and cellular glycolysis by activating AKT\/mTOR signaling pathway in HR+ breast cancer. Cell Death Discov. 2025;11:47.","journal-title":"Cell Death Discov"},{"key":"8435_CR105","doi-asserted-by":"crossref","unstructured":"Yokoyama T, Saitoh M, Miyazawa K. TGF-\u03b2 enhances doxorubicin resistance and anchorage-independent growth in cancer cells by inducing ALDH1A1 expression. Cancer Sci. 2025;116:2176\u201388.","DOI":"10.1111\/cas.70109"},{"key":"8435_CR106","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120682","volume":"303","author":"A Sharma","year":"2022","unstructured":"Sharma A, Thacker G, Mishra M, Singh AK, Upadhyay V, Sanyal S, et al. SOX4-mediated FBW7 transcriptional upregulation confers Tamoxifen resistance in ER+ breast cancers via GATA3 downregulation. Life Sci. 2022;303:120682.","journal-title":"Life Sci"},{"key":"8435_CR107","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.290","volume":"6","author":"R Sun","year":"2015","unstructured":"Sun R, Jiang B, Qi H, Zhang X, Yang J, Duan J, et al. SOX4 contributes to the progression of cervical cancer and the resistance to the chemotherapeutic drug through ABCG2. Cell Death Dis. 2015;6:e1990.","journal-title":"Cell Death Dis"},{"key":"8435_CR108","doi-asserted-by":"publisher","unstructured":"Qiong C, Fuguo Z. Inhibition of Sox4 increases the sensitivity of drug-resistant melanoma cells to cisplatin through the P38 signaling pathway. Comb Chem High Throughput Screen. 2025. https:\/\/doi.org\/10.2174\/0113862073231734231102074936.","DOI":"10.2174\/0113862073231734231102074936"},{"key":"8435_CR109","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.ccell.2020.12.001","volume":"39","author":"A Bagati","year":"2021","unstructured":"Bagati A, Kumar S, Jiang P, Pyrdol J, Zou AE, Godicelj A, et al. Integrin \u03b1v\u03b26-TGF\u03b2-SOX4 pathway drives immune evasion in triple-negative breast cancer. Cancer Cell. 2021;39:54\u201367.e9.","journal-title":"Cancer Cell"},{"key":"8435_CR110","doi-asserted-by":"publisher","unstructured":"Terranova CJ, Maitituoheti M, Raman AT, Tang M, Anvar NE, Ghosh AK, et al. H3K4me1-marked enhancer activation in resistant prostate cancers implicates SOX4 and MENIN inhibition as therapeutic strategies. 2021. https:\/\/doi.org\/10.1101\/2021.09.02.458625.","DOI":"10.1101\/2021.09.02.458625"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-026-08435-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-026-08435-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-026-08435-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:06:49Z","timestamp":1791950809000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-026-08435-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":110,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8435"],"URL":"https:\/\/doi.org\/10.1038\/s41419-026-08435-4","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,4]]},"assertion":[{"value":"26 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 December 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"All methods were performed in accordance with the relevant guidelines and regulations. This study does not include human subjects. The zebrafish experiments were performed at the Genome Engineering Zebrafish National Facility (currently DanioReadout, SciLifeLab Uppsala University), Sweden, that holds the appropriate ethical approval from the Swedish Board of Agriculture (5.8.18-10590\/2018 and 5.8.18-06282\/2023).","order":2,"name":"Ethics","label":"Ethical statement","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"209"}}