{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:59:06Z","timestamp":1791899946604,"version":"4.3.4"},"reference-count":68,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"11","license":[{"start":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T00:00:00Z","timestamp":1697673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173054"],"award-info":[{"award-number":["82173054"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81621004"],"award-info":[{"award-number":["81621004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81720108029"],"award-info":[{"award-number":["81720108029"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002782"],"award-info":[{"award-number":["82002782"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173054"],"award-info":[{"award-number":["82173054"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81621004"],"award-info":[{"award-number":["81621004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81720108029"],"award-info":[{"award-number":["81720108029"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002782"],"award-info":[{"award-number":["82002782"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515110069"],"award-info":[{"award-number":["2022A1515110069"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007162","name":"Guangdong Provincial Department of Science and Technology","doi-asserted-by":"publisher","award":["2022B1515020048"],"award-info":[{"award-number":["2022B1515020048"]}],"id":[{"id":"10.13039\/501100007162","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Commun"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">As a rapid\u2010progressing tumor, breast malignant phyllodes tumors (PTs) are challenged by the lack of effective therapeutic strategies and suitable prognostic markers. This study aimed to clarify the role and mechanism of CD146 on promoting PTs malignant progression, and to identify a novel prognosis marker and treatment target of breast malignant PTs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">The expression and prognostic significance of CD146 in PTs was detected through single\u2010cell RNA\u2010sequencing (scRNA\u2010seq), immunostaining, real\u2010time PCR and other methodologies. Functional experiments including proliferation assay, colony formation assay, transwell assay, and collagen contraction assay were conducted to validate the role of CD146 in malignant progression of PTs. The efficacy of anti\u2010CD146 monoclonal antibody AA98 against malignant PTs was corroborated by a malignant PT organoid model and a PT patient\u2010derived xenograft (PDX) model. Transcriptome sequencing, proteomic analysis, co\u2010immunoprecipitation, and pull\u2010down assay was employed to identify the modulating pathway and additional molecular mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      In this study, the scRNA\u2010seq analysis of PTs disclosed a CD146\u2010positive characteristic in the \u03b1\u2010SMA\n                      <jats:sup>+<\/jats:sup>\n                      fibroblast subset. Furthermore, a progressive elevation in the level of CD146 was observed with the malignant progression of PTs. More importantly, CD146 was found to serve as an independent predictor for recurrence in PT patients. Furthermore, CD146 was found to augment the viability and invasion of PTs. Mechanistically, CD146 acted as a protective \u201cshield\u201d to prevent the degradation of Discoidin, CUB, and LCCL domain\u2010containing protein 2 (DCBLD2), thereby activating the phosphoinositide 3\u2010kinase (PI3K)\/protein kinase B (AKT) signaling pathway and enhancing malignant behaviors of PT cells. In the malignant PT organoid and PDX model, a significant suppression of malignant PT growth was observed after the application of AA98.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">These findings suggested that CD146 served as an efficacious marker for predicting PT malignant progression and showed promise as a prognosis marker and treatment target of breast malignant PTs. The study further unveiled the essential role of the CD146\u2010DCBLD2\/PI3K\/AKT axis in the malignant progression of PTs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cac2.12495","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T13:16:44Z","timestamp":1697721404000},"page":"1244-1266","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["CD146 promotes malignant progression of breast phyllodes tumor through suppressing DCBLD2 degradation and activating the AKT pathway"],"prefix":"10.34133","volume":"43","author":[{"given":"Jiewen","family":"Chen","sequence":"first","affiliation":[{"name":"Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen Memorial Hospital","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen Memorial Hospital","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University","place":["Guangzhou, P. R. China"]},{"name":"Affiliated Foshan Maternity and Child Healthcare Hospital","place":["Foshan, P. R. China"]},{"name":"Southern Medical University","place":["Foshan, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9524-1848","authenticated-orcid":false,"given":"Qingji","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Biophysics","place":["Beijing, P. R. China"]},{"name":"Chinese Academy of Sciences","place":["Beijing, P. R. China"]},{"name":"University of Chinese Academy of Sciences","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Biophysics","place":["Beijing, P. R. China"]},{"name":"Chinese Academy of Sciences","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen Memorial Hospital","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen Memorial Hospital","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyan","family":"Guo","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen Memorial Hospital","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehui","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Biophysics","place":["Beijing, P. R. China"]},{"name":"Chinese Academy of Sciences","place":["Beijing, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyou","family":"Liao","sequence":"additional","affiliation":[{"name":"Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen Memorial Hospital","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Lei","sequence":"additional","affiliation":[{"name":"Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen Memorial Hospital","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen Memorial Hospital","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wende","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Laboratory Animal Monitoring Institute, Guangdong Key Laboratory of Laboratory Animal","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Huang","sequence":"additional","affiliation":[{"name":"Zhujiang Hospital","place":["Guangzhou, P. R. China"]},{"name":"Southern Medical University","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phei Er","family":"Saw","sequence":"additional","affiliation":[{"name":"Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen Memorial Hospital","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5400-9049","authenticated-orcid":false,"given":"Erwei","family":"Song","sequence":"additional","affiliation":[{"name":"Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen Memorial Hospital","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen Memorial Hospital","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyun","family":"Yan","sequence":"additional","affiliation":[{"name":"Institute of Biophysics","place":["Beijing, P. R. China"]},{"name":"Chinese Academy of Sciences","place":["Beijing, P. R. China"]},{"name":"University of Chinese Academy of Sciences","place":["Beijing, P. R. China"]},{"name":"Joint Laboratory of Nanozymes in Zhengzhou University","place":["Zhengzhou, P. R. China"]},{"name":"School of Basic Medical Sciences","place":["Zhengzhou, P. R. China"]},{"name":"Zhengzhou University","place":["Zhengzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1379-1353","authenticated-orcid":false,"given":"Yan","family":"Nie","sequence":"additional","affiliation":[{"name":"Guangdong\u2010Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen Memorial Hospital","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen Memorial Hospital","place":["Guangzhou, P. R. China"]},{"name":"Sun Yat\u2010sen University","place":["Guangzhou, P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"issue":"7","key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1002\/1097-0142(20001001)89:7<1502::AID-CNCR13>3.0.CO;2-P","article-title":"Primary treatment of cystosarcoma phyllodes of the breast","volume":"89","author":"Chaney AW","year":"2000","unstructured":"Chaney AW, Pollack A, McNeese MD, Zagars GK, Pisters PWT, Pollock RE, et\u00a0al. Primary treatment of cystosarcoma phyllodes of the breast. 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Ann Surg Oncol. 2007;14((10)):2961\u20132970.","journal-title":"Ann Surg Oncol"},{"issue":"3","key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1023\/A:1006260225618","article-title":"Histologic features predict local recurrence after breast conserving therapy of phyllodes tumors","volume":"57","author":"Barth RJ","year":"1999","unstructured":"Barth RJ Jr. Histologic features predict local recurrence after breast conserving therapy of phyllodes tumors. Breast Cancer Res Treat. 1999;57((3)):291\u2013295.","journal-title":"Breast Cancer Res Treat"},{"issue":"3","key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/j.1365-2559.1995.tb00212.x","article-title":"Phyllodes tumours of the breast: a clinicopathological review of thirty\u2010two cases","volume":"27","author":"Moffat CJ","year":"1995","unstructured":"Moffat CJ, Pinder SE, Dixon AR, Elston CW, Blamey RW, Ellis IO. Phyllodes tumours of the breast: a clinicopathological review of thirty\u2010two cases. Histopathology. 1995;27((3)):205\u2013218.","journal-title":"Histopathology"},{"issue":"909","key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1136\/pmj.77.909.428","article-title":"Phyllodes tumours","volume":"77","author":"Parker SJ","year":"2001","unstructured":"Parker SJ, Harries SA. Phyllodes tumours. Postgrad Med J. 2001;77((909)):428\u2013435.","journal-title":"Postgrad Med J"},{"issue":"16","key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"4341","DOI":"10.1158\/0008-5472.CAN-14-0125","article-title":"miR\u201021 induces myofibroblast differentiation and promotes the malignant progression of breast phyllodes tumors","volume":"74","author":"Gong C","year":"2014","unstructured":"Gong C, Nie Y, Qu S, Liao JY, Cui X, Yao H, et\u00a0al. miR\u201021 induces myofibroblast differentiation and promotes the malignant progression of breast phyllodes tumors. Cancer Res. 2014;74((16)):4341\u20134352.","journal-title":"Cancer Res"},{"issue":"2","key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.canlet.2012.11.049","article-title":"CD146, a multi\u2010functional molecule beyond adhesion","volume":"330","author":"Wang Z","year":"2013","unstructured":"Wang Z, Yan X. CD146, a multi\u2010functional molecule beyond adhesion. Cancer Lett. 2013;330((2)):150\u2013162.","journal-title":"Cancer Lett"},{"issue":"3","key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/sj.leu.2400922","article-title":"MUC18, a member of the immunoglobulin superfamily, is expressed on bone marrow fibroblasts and a subset of hematological malignancies","volume":"12","author":"Filshie RJ","year":"1998","unstructured":"Filshie RJ, Zannettino AC, Makrynikola V, Gronthos S, Henniker AJ, Bendall LJ, et\u00a0al. 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Cancer Sci. 2013;104((8)):989\u2013995.","journal-title":"Cancer Sci"},{"issue":"13","key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"3873","DOI":"10.1158\/1078-0432.CCR-18-3421","article-title":"Breast phyllodes tumors recruit and repolarize tumor\u2010associated macrophages via secreting CCL5 to promote malignant progression, which can be inhibited by CCR5 inhibition therapy","volume":"25","author":"Nie Y","year":"2019","unstructured":"Nie Y, Huang H, Guo M, Chen J, Wu W, Li W, et\u00a0al. Breast phyllodes tumors recruit and repolarize tumor\u2010associated macrophages via secreting CCL5 to promote malignant progression, which can be inhibited by CCR5 inhibition therapy. Clin Cancer Res. 2019;25((13)):3873\u20133886.","journal-title":"Clin Cancer Res"},{"issue":"4","key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1093\/jnci\/djz134","article-title":"The role of APAL\/ST8SIA6\u2010AS1 lncRNA in PLK1 activation and mitotic catastrophe of tumor cells","volume":"112","author":"Luo ML","year":"2020","unstructured":"Luo ML, Li J, Shen L, Chu J, Guo Q, Liang G, et\u00a0al. The role of APAL\/ST8SIA6\u2010AS1 lncRNA in PLK1 activation and mitotic catastrophe of tumor cells. 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Breast Cancer Res. 2014;16((2)):R29.","journal-title":"Breast Cancer Res"},{"issue":"4","key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1111\/his.13782","article-title":"Expression of biomarkers in the AKT pathway correlates with malignancy and recurrence in phyllodes tumours of the breast","volume":"74","author":"Li J","year":"2019","unstructured":"Li J, Ho W\u2010Y, Tsang JYS, Ni Y\u2010B, Chan S\u2010K, Tse GM. Expression of biomarkers in the AKT pathway correlates with malignancy and recurrence in phyllodes tumours of the breast. Histopathology. 2019;74((4)):567\u2013577.","journal-title":"Histopathology"},{"issue":"10","key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"9041","DOI":"10.3390\/ijms24109041","article-title":"Gene Expression Profiling of Fibroepithelial Lesions of the Breast","volume":"24","author":"Li X","year":"2023","unstructured":"Li X, Vail E, Maluf H, Chaum M, Leong M, Lownik J, et\u00a0al. 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