{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:11:23Z","timestamp":1791655883967,"version":"4.3.4"},"reference-count":79,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"14","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R37CA269783-01A1"],"award-info":[{"award-number":["R37CA269783-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32CA203690"],"award-info":[{"award-number":["T32CA203690"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["RSG-22-093-01-CCB"],"award-info":[{"award-number":["RSG-22-093-01-CCB"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["PF-24-1293970-01-TBE"],"award-info":[{"award-number":["PF-24-1293970-01-TBE"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP150148"],"award-info":[{"award-number":["RP150148"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP160710"],"award-info":[{"award-number":["RP160710"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RR200009"],"award-info":[{"award-number":["RR200009"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,4,3]]},"abstract":"<jats:p>Systemic neoadjuvant chemotherapy, often combined with immunotherapy, is the standard of care for early-stage, non\u2013breast cancer susceptibility gene (BRCA)-mutant triple negative breast cancer (TNBC). However, up to 70% of patients retain residual disease after treatment, which is linked to recurrence and mortality within 5 years. To define mechanisms of resistance, we performed single-cell RNA sequencing on orthotopic TNBC patient-derived xenografts during a cycle of treatment with doxorubicin and cyclophosphamide (AC). Clustering identified four tumor epithelial cell populations, with basal cells enriched in residual tumors. These basal cells up-regulated C15ORF48, a paralog of the mitochondrial cytochrome c oxidase associated subunit FA4 (NDUFA4), while exhibiting reciprocal down-regulation of NDUFA4. Functionally, C15ORF48 knockdown sensitized breast cancer cells to AC, increasing reactive oxygen species (ROS) and apoptosis. Thus, the up-regulation of C15ORF48 blunts ROS accumulation and induces resistance to chemotherapy in the basal cell subpopulations. Our findings identify C15ORF48 as a potential therapeutic target for overcoming AC resistance in TNBC.<\/jats:p>","DOI":"10.1126\/sciadv.aec8684","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T17:58:57Z","timestamp":1775239137000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Regulation of mitochondrial ROS by C15ORF48 in a basal cell subpopulation contributes to chemotherapy resistance in TNBC"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1945-4200","authenticated-orcid":true,"given":"Yan","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0189-3069","authenticated-orcid":true,"given":"Noor M.","family":"Abdulkareem","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3276-6863","authenticated-orcid":true,"given":"Amanda L.","family":"Rinkenbaugh","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9718-7593","authenticated-orcid":true,"given":"Yuan","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA."},{"name":"Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4813-9920","authenticated-orcid":true,"given":"Steven W.","family":"Wall","sequence":"additional","affiliation":[{"name":"Lester and Sue Smith Breast Cancer Center and Department of Medicine, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0964-8922","authenticated-orcid":true,"given":"Xiaomei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5264-2219","authenticated-orcid":true,"given":"Jiansu","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9254-4499","authenticated-orcid":true,"given":"Sabrina","family":"Jeter-Jones","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirong","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7567-8567","authenticated-orcid":true,"given":"Faiza Baameur","family":"Hancock","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3772-9298","authenticated-orcid":true,"given":"Gloria V.","family":"Echeverria","sequence":"additional","affiliation":[{"name":"Lester and Sue Smith Breast Cancer Center and Department of Medicine, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4578-5636","authenticated-orcid":true,"given":"Jeffrey T.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA."},{"name":"Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4210-6738","authenticated-orcid":true,"given":"Helen","family":"Piwnica-Worms","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-3045"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/35021093"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-042420-093238"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.03399"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00589-1"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3347-1_1"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-00302-4"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.13601"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav0936"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.597434"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.09.021"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c00967"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-024-03025-0"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2024.06.012"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31031-2"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07406-4"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3934\/mbe.2022271"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2020.12.018"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06052-0"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44321-024-00050-0"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2025.02.038"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1436420"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202309903"},{"key":"e_1_3_2_26_2","first-page":"751","article-title":"Basal cell-specific and hyperproliferation-related keratins in human breast cancer","volume":"138","author":"Wetzels R. H.","year":"1991","unstructured":"R. H. Wetzels, H. J. Kuijpers, E. B. Lane, I. M. Leigh, S. M. Troyanovsky, R. Holland, U. J. van Haelst, F. C. Ramaekers, Basal cell-specific and hyperproliferation-related keratins in human breast cancer. Am. J. Pathol. 138, 751\u2013763 (1991).","journal-title":"Am. J. Pathol."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-021-00374-9"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.108805"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1080\/19336918.2022.2072554"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI138577"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abl5182"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22397-5"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45206-1"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.616190"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.205278"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.09.033"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-24-5023"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.7150\/jca.18457"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.06.010"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25179482"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.01.007"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-024-02917-y"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.101973"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-82218-9"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-024-03318-3"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0297260"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25136853"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241814188"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2021.09.002"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-020-00383-y"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-020-05936-4"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.041"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.928175"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-020-01736-2"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2025.114455"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1131870"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw951"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1092"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.027"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1254313"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-023-02596-8"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-06077-2"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20081386"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1139\/bcb-2023-0018"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-022-09949-0"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-24-0512"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01313-4"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-016-9653-x"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"e_1_3_2_72_2","unstructured":"G. Korotkevich V. Sukhov N. Budin B. Shpak M. N. Artyomov A. Sergushichev Fast gene set enrichment analysis. bioRxiv 060012 (2021). www.biorxiv.org\/content\/10.1101\/060012v3."},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157368"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-024-00644-4"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw817"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts236"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aec8684","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T17:59:07Z","timestamp":1775239147000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aec8684"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,3]]},"references-count":79,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2026,4,3]]}},"alternative-id":["10.1126\/sciadv.aec8684"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aec8684","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,3]]},"assertion":[{"value":"2025-10-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaec8684"}}