{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:41Z","timestamp":1790208041973,"version":"4.1.0"},"reference-count":27,"publisher":"National Academy of Sciences","issue":"21","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100010788","name":"International Cancer Imaging Society","doi-asserted-by":"publisher","award":["R01CA193455"],"award-info":[{"award-number":["R01CA193455"]}],"id":[{"id":"10.13039\/100010788","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2021,5,25]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    HER2\n                    <jats:sup>+<\/jats:sup>\n                    breast cancers (BrCs) are heterogeneous, but they are treated as a single type. Using a mouse model with Erbb2 (the rodent homolog of HER2)-induced BrC and cell lineage-tracing capacity, we found that ER\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    Erbb2\n                    <jats:sup>+<\/jats:sup>\n                    cancer cells proliferate slowly and are nonmetastatic but then progressively lose ER\u03b1 expression to become fast proliferating and highly metastatic ER\u03b1\n                    <jats:sup>\u2212<\/jats:sup>\n                    Erbb2\n                    <jats:sup>+<\/jats:sup>\n                    cancer cells. ER\u03b1\n                    <jats:sup>\u2212<\/jats:sup>\n                    Erbb2\n                    <jats:sup>+<\/jats:sup>\n                    cancer cells with an ER\u03b1\n                    <jats:sup>\u2212<\/jats:sup>\n                    origin proliferate fast, but they metastasize weakly. These findings suggest: 1) ER\u03b1 expression should be preserved in ER\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    HER2\n                    <jats:sup>+<\/jats:sup>\n                    BrCs to restrict growth and metastasis; 2) ER\u03b1\n                    <jats:sup>\u2212<\/jats:sup>\n                    HER2\n                    <jats:sup>+<\/jats:sup>\n                    BrCs contain a highly metastatic subtype with an ER\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    origin and a weakly metastatic subtype with an ER\u03b1\n                    <jats:sup>\u2212<\/jats:sup>\n                    origin, indicating a future need to identify and differentially treat these two subtypes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2100673118","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T16:05:53Z","timestamp":1621353953000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["Cell lineage tracing links ER\u03b1 loss in Erbb2-positive breast cancers to the arising of a highly aggressive breast cancer subtype"],"prefix":"10.1073","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6592-1159","authenticated-orcid":false,"given":"Yunfeng","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-7720","authenticated-orcid":false,"given":"Yonghong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9063-9048","authenticated-orcid":false,"given":"Dong-Kee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangwei","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9727-351X","authenticated-orcid":false,"given":"Xiaobin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9976-518X","authenticated-orcid":false,"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"},{"name":"Children\u2019s Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1713-8527","authenticated-orcid":false,"given":"Rainer B.","family":"Lanz","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-1399","authenticated-orcid":false,"given":"Bert W.","family":"O\u2019Malley","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8208-9162","authenticated-orcid":false,"given":"Jianming","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,5,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002069"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00665980"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.01.172"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-031212"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66544-0"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.9820"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-014-2983-x"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.9437"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052306"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61847-3"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.62.1268"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0299-9"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-2707"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-018-2644-2"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25506"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.37.2482"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13169"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636745"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608607103"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1618091114"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1988.tb03044.x"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.043299"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-0746"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27431"},{"key":"e_1_3_4_25_2","first-page":"4987","article-title":"Dissociation between steroid receptor expression and cell proliferation in the human breast","volume":"57","author":"Clarke R. B.","year":"1997","unstructured":"R. B. Clarke, A. Howell, C. S. Potten, E. Anderson, Dissociation between steroid receptor expression and cell proliferation in the human breast. Cancer Res. 57, 4987\u20134991 (1997).","journal-title":"Cancer Res."},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808703105"},{"key":"e_1_3_4_27_2","unstructured":"Y. Ding J. Xu RNA-Seq profiling of ER-\/Erbb2+ mouse breast cancer cells with ER+ and ER- cellular origins. BioProject category of the NCBI Sequence Read Archive database. https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/?term=PRJNA713819 (Deposited 12 March 2021)."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2100673118","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2100673118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T08:28:36Z","timestamp":1649838516000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2100673118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,18]]},"references-count":27,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2021,5,25]]}},"alternative-id":["10.1073\/pnas.2100673118"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2100673118","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,18]]},"assertion":[{"value":"2021-05-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2100673118"}}