{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:09:09Z","timestamp":1785413349946,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,16]]},"group-title":"Cancer Biology","reference-count":64,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:00:00Z","timestamp":1778889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["1R01CA226269"],"award-info":[{"award-number":["1R01CA226269"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01CA271588"],"award-info":[{"award-number":["R01CA271588"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U24CA274212"],"award-info":[{"award-number":["U24CA274212"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P20GM130423"],"award-info":[{"award-number":["P20GM130423"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Ductal carcinoma in situ (DCIS) exhibits substantial heterogeneity in its risk of progression to invasive breast cancer, yet the cellular and molecular determinants of high-risk lesions remain incompletely defined. Using spatially resolved single-cell transcriptomic and epigenomic profiling of 43 patient-derived DCIS and DCIS\/invasive ductal carcinoma (IDC) samples, we delineate cellular programs, spatial organization, and epigenetic regulatory mechanisms associated with invasive potential. We identify an epithelial population with stemness features within luminal hormone-responsive (LumHR) cells that progressively expands from benign tissue to DCIS and IDC, and is strongly associated with invasive progression and recurrence-linked transcriptional programs. Spatial mapping reveals discrete DCIS niches enriched for stem-like LumHR cells, characterized by elevated CEACAM6 expression and enhanced ligand\u2013receptor interactions, including CEACAM6\u2013EGFR signaling between epithelial and stromal compartments, including cancer-associated fibroblasts, macrophages (\n                  <jats:italic>APOC1<\/jats:italic>\n                  -positive) and perivascular cells. These niches define a microenvironmental context that supports stemness and invasive potential. Epigenomic analyses implicate FOXA1 as a key regulator of these stem-like transcriptional states. Pharmacologic disruption of FOXA1-regulatory network using LSD1 inhibition suppresses stemness-associated transcriptional programs in vitro and significantly restrains tumor growth in vivo. Collectively, these findings define high-risk DCIS as a stemness-driven disease embedded within specialized microenvironments, and identify associated regulatory networks as candidate biomarkers and therapeutic vulnerabilities.\n                <\/jats:p>","DOI":"10.64898\/2026.05.13.724882","type":"posted-content","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T14:10:27Z","timestamp":1778940627000},"source":"Crossref","is-referenced-by-count":0,"title":["Cellular stemness identifies high-risk ductal carcinoma\n                  <i>in situ<\/i>\n                  and offers a therapeutic interception opportunity"],"prefix":"10.64898","author":[{"given":"E.","family":"Schueddig","sequence":"first","affiliation":[{"name":"Department of Biostatistics & Data Science, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Kochat","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and MDACC Epigenomics Therapy Initiative, The University of Texas MD Anderson Cancer Center,1515 Holcombe Boulevard, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Arslan","sequence":"additional","affiliation":[{"name":"Oncology Research and Development, Takeda Pharmaceuticals, 650 East Kendall Street, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Dallas","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center,1515 Holcombe Boulevard, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Padron","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and MDACC Epigenomics Therapy Initiative, The University of Texas MD Anderson Cancer Center,1515 Holcombe Boulevard, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center,1515 Holcombe Boulevard, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Henry","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, The University of Texas MD Anderson Cancer Center,1515 Holcombe Boulevard, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Mattohti","sequence":"additional","affiliation":[{"name":"Department of Surgery, Immunobiology and Transplant Science Center, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX 77030, USA"},{"name":"Department of Surgery, Weill Cornell Medicine, Cornell Univeristy New York, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Madan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Fields","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Golem","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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