{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:51:26Z","timestamp":1779195086658,"version":"3.51.4"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Cancer Institute","award":["P50CA062924"],"award-info":[{"award-number":["P50CA062924"]}]},{"name":"National Cancer Institute","award":["P30CA013330"],"award-info":[{"award-number":["P30CA013330"]}]},{"name":"National Cancer Institute","award":["P50CA062924"],"award-info":[{"award-number":["P50CA062924"]}]},{"name":"National Cancer Institute","award":["P30CA014089"],"award-info":[{"award-number":["P30CA014089"]}]},{"name":"The Commonwealth Foundation for Cancer Research"},{"name":"The Allegheny Foundation"},{"name":"The Integrated Imaging Program for Cancer Research IIPCR"},{"name":"The Evelyn-Lipper Charitable Foundation"},{"name":"The Montefiore-Einstein Comprehensive Cancer Center (MECC) start-up fund"},{"name":"The EGL Charitable Foundation"},{"name":"The Emerson Foundation"},{"name":"Tower Cancer Research Foundation Career Development Award"},{"name":"Concern Foundation Conquer Cancer Now Award"},{"DOI":"10.13039\/100006034","name":"University of Southern California","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006034","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Metastasis"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Metastatic disease results from the dissemination of tumor cells beyond their organ of origin to grow in distant organs and is the primary cause of death in patients with advanced breast cancer. Preclinical murine models in which primary tumors spontaneously metastasize are valuable tools for studying metastatic progression and novel cancer treatment combinations. Here, we characterize a novel syngeneic murine breast tumor cell line that provides a model of spontaneously metastatic neu-expressing breast cancer with quicker onset of widespread metastases after orthotopic mammary implantation in immune-competent NeuN mice. The NT2.5-lung metastasis (-LM) cell line was derived from serial passaging of tumor cells that were macro-dissected from spontaneous lung metastases after orthotopic mammary implantation of parental NT2.5 cells. Within one week of NT2.5-LM implantation, metastases are observed in the lungs. Within four weeks, metastases are also observed in the bones, spleen, colon, and liver. We demonstrate that NT2.5-LM metastases are positive for NeuN\u2014the murine equivalent of human epidermal growth factor 2 (HER2). We further demonstrate altered expression of markers of epithelial-to-mesenchymal transition (EMT), suggestive of their enhanced metastatic potential. Genomic analyses support these findings and reveal enrichment in EMT-regulating pathways. In addition, the metastases are rapidly growing, proliferative, and responsive to HER2-directed therapy. The new NT2.5-LM model provides certain advantages over the parental NT2\/NT2.5 model, given its more rapid and spontaneous development of metastases. Besides investigating mechanisms of metastatic progression, this new model may be used for the rationalized development of novel therapeutic interventions and assessment of therapeutic responses.<\/jats:p>","DOI":"10.1007\/s10585-024-10289-z","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:01:38Z","timestamp":1715126498000},"page":"733-746","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A new Neu\u2014a syngeneic model of spontaneously metastatic HER2-positive breast cancer"],"prefix":"10.1007","volume":"41","author":[{"given":"Aaron G.","family":"Baugh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edgar","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie H.","family":"Narumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesse","family":"Kreger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingtong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Rafie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofi","family":"Castanon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Jang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciane T.","family":"Kagohara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitra P.","family":"Anastasiadou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Leatherman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isaac","family":"Chan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George S.","family":"Karagiannis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth M.","family":"Jaffee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"MacLean","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evanthia T.","family":"Roussos Torres","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"issue":"3","key":"10289_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/CAAC.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209\u2013249. https:\/\/doi.org\/10.3322\/CAAC.21660","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"10289_CR2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41416-020-01161-4","volume":"124","author":"AI Riggio","year":"2020","unstructured":"Riggio AI, Varley KE, Welm AL (2020) The lingering mysteries of metastatic recurrence in breast cancer. Br J Cancer 124(1):13\u201326. https:\/\/doi.org\/10.1038\/s41416-020-01161-4","journal-title":"Br J Cancer"},{"issue":"4","key":"10289_CR3","doi-asserted-by":"publisher","first-page":"160","DOI":"10.5625\/LAR.2018.34.4.160","volume":"34","author":"MK Park","year":"2018","unstructured":"Park MK, Lee CH, Lee H (2018) Mouse models of breast cancer in preclinical research. Lab Anim Res 34(4):160. https:\/\/doi.org\/10.5625\/LAR.2018.34.4.160","journal-title":"Lab Anim Res"},{"issue":"3","key":"10289_CR4","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/J.BBRC.2010.03.070","volume":"394","author":"IS Kim","year":"2010","unstructured":"Kim IS, Baek SH (2010) Mouse models for breast cancer metastasis. Biochem Biophys Res Commun 394(3):443\u2013447. https:\/\/doi.org\/10.1016\/J.BBRC.2010.03.070","journal-title":"Biochem Biophys Res Commun"},{"key":"10289_CR5","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1002\/(SICI)1096-9896(199901)187:1","volume":"187","author":"KF Macleod","year":"1999","unstructured":"Macleod KF, Jacks T (1999) Insights into cancer from transgenic mouse models. J Pathol 187:43\u201360. https:\/\/doi.org\/10.1002\/(SICI)1096-9896(199901)187:1","journal-title":"J Pathol"},{"issue":"8","key":"10289_CR6","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1038\/SJ.ONC.1203280","volume":"19","author":"JE Green","year":"2000","unstructured":"Green JE et al (2000) The C3(1)\/SV40 T-antigen transgenic mouse model of mammary cancer: ductal epithelial cell targeting with multistage progression to carcinoma. Oncogene 19(8):1020\u20131027. https:\/\/doi.org\/10.1038\/SJ.ONC.1203280","journal-title":"Oncogene"},{"issue":"14","key":"10289_CR7","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 (2003) Transforming growth factor \u03b2 signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. Proc Natl Acad Sci U S A 100(14):8430. https:\/\/doi.org\/10.1073\/PNAS.0932636100","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"10289_CR8","doi-asserted-by":"publisher","first-page":"3525","DOI":"10.1158\/0008-5472.CAN-03-3524","volume":"64","author":"SCJ Lin","year":"2004","unstructured":"Lin SCJ et al (2004) Somatic mutation of p53 leads to estrogen receptor alpha-positive and -negative mouse mammary tumors with high frequency of metastasis. Cancer Res 64(10):3525\u20133532. https:\/\/doi.org\/10.1158\/0008-5472.CAN-03-3524","journal-title":"Cancer Res"},{"issue":"22","key":"10289_CR9","doi-asserted-by":"publisher","first-page":"10578","DOI":"10.1073\/PNAS.89.22.10578","volume":"89","author":"CT Guy","year":"1992","unstructured":"Guy CT, Webster MA, Schaller M, Parsons TJ, Cardiff RD, Muller WJ (1992) Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci 89(22):10578\u201310582. https:\/\/doi.org\/10.1073\/PNAS.89.22.10578","journal-title":"Proc Natl Acad Sci"},{"issue":"3","key":"10289_CR10","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1128\/MCB.12.3.954","volume":"12","author":"CT Guy","year":"1992","unstructured":"Guy CT, Cardiff RD, Muller WJ (1992) Induction of mammary tumors by expression of polyomavirus middle T oncogene a transgenic mouse model for metastatic disease. Mol Cell Biol 12(3):954. https:\/\/doi.org\/10.1128\/MCB.12.3.954","journal-title":"Mol Cell Biol"},{"issue":"3","key":"10289_CR11","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1002\/IJC.30399","volume":"140","author":"EA Fry","year":"2017","unstructured":"Fry EA, Taneja P, Inoue K (2017) Oncogenic and tumor-suppressive mouse models for breast cancer engaging HER2\/neu. Int J Cancer 140(3):495\u2013503. https:\/\/doi.org\/10.1002\/IJC.30399","journal-title":"Int J Cancer"},{"issue":"19","key":"10289_CR12","doi-asserted-by":"publisher","first-page":"6116","DOI":"10.1158\/1078-0432.CCR-07-4672","volume":"14","author":"H Song","year":"2008","unstructured":"Song H et al (2008) An immunotolerant HER-2\/neu transgenic mouse model of metastatic breast cancer. Clin Cancer Res 14(19):6116. https:\/\/doi.org\/10.1158\/1078-0432.CCR-07-4672","journal-title":"Clin Cancer Res"},{"issue":"13","key":"10289_CR13","first-page":"3569","volume":"60","author":"RT Reilly","year":"2000","unstructured":"Reilly RT et al (2000) HER-2\/neu is a tumor rejection target in tolerized HER-2\/neu transgenic mice. Cancer Res 60(13):3569\u20133576","journal-title":"Cancer Res"},{"issue":"9","key":"10289_CR14","first-page":"3689","volume":"61","author":"JP Machiels","year":"2001","unstructured":"Machiels JP et al (2001) Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte\/macrophage-colony stimulating factor-secreting whole-cell vaccines in HER-2\/neu tolerized mice. Cancer Res 61(9):3689\u20133697","journal-title":"Cancer Res"},{"issue":"3","key":"10289_CR15","first-page":"194","volume":"4","author":"EM Jaffee","year":"1998","unstructured":"Jaffee EM et al (1998) Development and characterization of a cytokine-secreting pancreatic adenocarcinoma vaccine from primary tumors for use in clinical trials. Cancer J Sci Am 4(3):194\u2013203","journal-title":"Cancer J Sci Am"},{"issue":"12","key":"10289_CR16","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1158\/2326-6066.CIR-18-0070","volume":"6","author":"BJ Christmas","year":"2018","unstructured":"Christmas BJ et al (2018) Entinostat converts immune-resistant breast and pancreatic cancers into checkpoint-responsive tumors by reprogramming tumor-infiltrating MDSCs. Cancer Immunol Res 6(12):1561\u20131577. https:\/\/doi.org\/10.1158\/2326-6066.CIR-18-0070","journal-title":"Cancer Immunol Res"},{"issue":"2","key":"10289_CR17","doi-asserted-by":"publisher","first-page":"355","DOI":"10.3892\/MCO.2016.919","volume":"5","author":"UR G\u00fcnd\u00fcz","year":"2016","unstructured":"G\u00fcnd\u00fcz UR, Gunaldi M, Isiksacan N, G\u00fcnd\u00fcz S, Okuturlar Y, Kocoglu H (2016) A new marker for breast cancer diagnosis, human epididymis protein 4: A preliminary study. Mol Clin Oncol 5(2):355. https:\/\/doi.org\/10.3892\/MCO.2016.919","journal-title":"Mol Clin Oncol"},{"issue":"4","key":"10289_CR18","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/J.CCELL.2017.03.005","volume":"31","author":"S Seaman","year":"2017","unstructured":"Seaman S et al (2017) Eradication of Tumors through Simultaneous Ablation of CD276\/B7-H3 Positive Tumor Cells and Tumor Vasculature. Cancer Cell 31(4):501. https:\/\/doi.org\/10.1016\/J.CCELL.2017.03.005","journal-title":"Cancer Cell"},{"issue":"10","key":"10289_CR19","doi-asserted-by":"publisher","first-page":"3913","DOI":"10.1073\/PNAS.0810617106\/SUPPL_FILE\/0810617106SI.PDF","volume":"106","author":"J Yang","year":"2009","unstructured":"Yang J et al (2009) Lipocalin 2 promotes breast cancer progression. Proc Natl Acad Sci USA 106(10):3913\u20133918. https:\/\/doi.org\/10.1073\/PNAS.0810617106\/SUPPL_FILE\/0810617106SI.PDF","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7","key":"10289_CR20","doi-asserted-by":"publisher","first-page":"2995","DOI":"10.1073\/PNAS.1000101107\/SUPPL_FILE\/PNAS.201000101SI.PDF","volume":"107","author":"T Berger","year":"2010","unstructured":"Berger T, Cheung CC, Elia AJ, Mak TW (2010) Disruption of the Lcn2 gene in mice suppresses primary mammary tumor formation but does not decrease lung metastasis. Proc Natl Acad Sci USA 107(7):2995\u20133000. https:\/\/doi.org\/10.1073\/PNAS.1000101107\/SUPPL_FILE\/PNAS.201000101SI.PDF","journal-title":"Proc Natl Acad Sci USA"},{"key":"10289_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7554\/ELIFE.58810","volume":"9","author":"SK Yeo","year":"2020","unstructured":"Yeo SK et al (2020) Single-cell RNA-sequencing reveals distinct patterns of cell state heterogeneity in mouse models of breast cancer. Elife 9:1\u201324. https:\/\/doi.org\/10.7554\/ELIFE.58810","journal-title":"Elife"},{"issue":"5","key":"10289_CR22","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1158\/2326-6066.CIR-21-0170","volume":"10","author":"DN Sidiropoulos","year":"2022","unstructured":"Sidiropoulos DN et al (2022) Entinostat decreases immune suppression to promote anti-tumor responses in a HER2+ breast tumor microenvironment. Cancer Immunol Res 10(5):565\u2013669. https:\/\/doi.org\/10.1158\/2326-6066.CIR-21-0170","journal-title":"Cancer Immunol Res"},{"issue":"6","key":"10289_CR23","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1158\/2326-6066.CIR-21-0804","volume":"10","author":"CR Gil Del Alcazar","year":"2022","unstructured":"Gil Del Alcazar CR et al (2022) Insights into Immune Escape During Tumor Evolution and Response to Immunotherapy Using a Rat Model of Breast Cancer. Cancer Immunol Res 10(6):680. https:\/\/doi.org\/10.1158\/2326-6066.CIR-21-0804","journal-title":"Cancer Immunol Res"},{"issue":"1","key":"10289_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-735","volume":"14","author":"MP Pinto","year":"2014","unstructured":"Pinto MP, Dye WW, Jacobsen BM, Horwitz KB (2014) Malignant stroma increases luminal breast cancer cell proliferation and angiogenesis through platelet-derived growth factor signaling. BMC Cancer 14(1):735. https:\/\/doi.org\/10.1186\/1471-2407-14-735","journal-title":"BMC Cancer"},{"issue":"2","key":"10289_CR25","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/S10549-018-4664-7","volume":"169","author":"S Jansson","year":"2018","unstructured":"Jansson S et al (2018) The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence. Breast Cancer Res Treat 169(2):231. https:\/\/doi.org\/10.1007\/S10549-018-4664-7","journal-title":"Breast Cancer Res Treat"},{"issue":"12","key":"10289_CR26","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1158\/1541-7786.MCR-19-0311","volume":"18","author":"Y Ma","year":"2020","unstructured":"Ma Y et al (2020) SOX9 Is essential for triple-negative breast cancer cell survival and metastasis. Mol Cancer Res 18(12):1825\u20131838. https:\/\/doi.org\/10.1158\/1541-7786.MCR-19-0311","journal-title":"Mol Cancer Res"},{"issue":"1","key":"10289_CR27","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/S40880-015-0064-0","volume":"35","author":"P Xing","year":"2016","unstructured":"Xing P et al (2016) Roles of low-density lipoprotein receptor-related protein 1 in tumors. Chin J Cancer 35(1):6. https:\/\/doi.org\/10.1186\/S40880-015-0064-0","journal-title":"Chin J Cancer"},{"issue":"14","key":"10289_CR28","doi-asserted-by":"publisher","first-page":"5690","DOI":"10.1158\/0008-5472.CAN-08-4573","volume":"69","author":"B Fayard","year":"2009","unstructured":"Fayard B et al (2009) The serine protease inhibitor protease nexin-1 controls mammary cancer metastasis through LRP-1-mediated MMP-9 expression. Cancer Res 69(14):5690\u20135698. https:\/\/doi.org\/10.1158\/0008-5472.CAN-08-4573","journal-title":"Cancer Res"},{"issue":"10","key":"10289_CR29","doi-asserted-by":"publisher","first-page":"7970","DOI":"10.18632\/ONCOTARGET.3419","volume":"6","author":"G Rappa","year":"2015","unstructured":"Rappa G, Green TM, Karbanov\u00e1 J, Corbeil D, Lorico A (2015) Tetraspanin CD9 determines invasiveness and tumorigenicity of human breast cancer cells. Oncotarget 6(10):7970. https:\/\/doi.org\/10.18632\/ONCOTARGET.3419","journal-title":"Oncotarget"},{"issue":"3","key":"10289_CR30","doi-asserted-by":"publisher","first-page":"684","DOI":"10.3892\/IJO.2019.4840","volume":"55","author":"C Yang","year":"2019","unstructured":"Yang C et al (2019) CXCL1 stimulates migration and invasion in ER-negative breast cancer cells via activation of the ERK\/MMP2\/9 signaling axis. Int J Oncol 55(3):684\u2013696. https:\/\/doi.org\/10.3892\/IJO.2019.4840","journal-title":"Int J Oncol"},{"issue":"5","key":"10289_CR31","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1080\/19336918.2018.1486143","volume":"12","author":"LA Moraes","year":"2018","unstructured":"Moraes LA, Ampomah PB, Lim LHK (2018) Annexin A1 in inflammation and breast cancer: a new axis in the tumor microenvironment. Cell Adh Migr 12(5):417. https:\/\/doi.org\/10.1080\/19336918.2018.1486143","journal-title":"Cell Adh Migr"},{"issue":"10","key":"10289_CR32","doi-asserted-by":"publisher","first-page":"2691","DOI":"10.1002\/JCP.22620","volume":"226","author":"A Baillo","year":"2011","unstructured":"Baillo A, Giroux C, Ethier SP (2011) Knock-down of amphiregulin inhibits cellular invasion in inflammatory breast cancer. J Cell Physiol 226(10):2691\u20132701. https:\/\/doi.org\/10.1002\/JCP.22620","journal-title":"J Cell Physiol"},{"issue":"1","key":"10289_CR33","doi-asserted-by":"publisher","first-page":"171","DOI":"10.3892\/OR.2013.2428","volume":"30","author":"M Yang","year":"2013","unstructured":"Yang M, Gao H, Chen P, Jia J, Wu S (2013) Knockdown of interferon-induced transmembrane protein 3 expression suppresses breast cancer cell growth and colony formation and affects the cell cycle. Oncol Rep 30(1):171\u2013178. https:\/\/doi.org\/10.3892\/OR.2013.2428","journal-title":"Oncol Rep"},{"key":"10289_CR34","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/J.BIOCHI.2022.02.003","volume":"197","author":"D Paulin","year":"2022","unstructured":"Paulin D, Lilienbaum A, Kardjian S, Agbulut O, Li Z (2022) Vimentin: Regulation and pathogenesis. Biochimie 197:96\u2013112. https:\/\/doi.org\/10.1016\/J.BIOCHI.2022.02.003","journal-title":"Biochimie"},{"issue":"1","key":"10289_CR35","doi-asserted-by":"publisher","first-page":"4681","DOI":"10.1080\/21655979.2021.1957754","volume":"12","author":"Y Yu","year":"2021","unstructured":"Yu Y, Wang W, Lu W, Chen W, Shang A (2021) Inhibin \u03b2-A (INHBA) induces epithelial\u2013mesenchymal transition and accelerates the motility of breast cancer cells by activating the TGF-\u03b2 signaling pathway. Bioengineered 12(1):4681. https:\/\/doi.org\/10.1080\/21655979.2021.1957754","journal-title":"Bioengineered"},{"issue":"11","key":"10289_CR36","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1038\/sj.bjc.6602613","volume":"92","author":"DM Helfman","year":"2005","unstructured":"Helfman DM, Kim EJ, Lukanidin E, Grigorian M (2005) The metastasis associated protein S100A4: role in tumour progression and metastasis. Br J Cancer 92(11):1955\u20131958. https:\/\/doi.org\/10.1038\/sj.bjc.6602613","journal-title":"Br J Cancer"},{"issue":"528","key":"10289_CR37","doi-asserted-by":"publisher","DOI":"10.1126\/SCISIGNAL.AAO6897\/SUPPL_FILE\/AAO6897_SM.PDF","volume":"11","author":"AL Elaimy","year":"2018","unstructured":"Elaimy AL et al (2018) VEGF-neuropilin-2 signaling promotes stem-like traits in breast cancer cells by TAZ-mediated repression of the Rac GAP \u03b22-chimaerin. Sci Signal 11(528):eaao6897. https:\/\/doi.org\/10.1126\/SCISIGNAL.AAO6897\/SUPPL_FILE\/AAO6897_SM.PDF","journal-title":"Sci Signal"},{"issue":"1","key":"10289_CR38","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/1471-2407-9-220\/FIGURES\/4","volume":"9","author":"H Yasuoka","year":"2009","unstructured":"Yasuoka H et al (2009) Neuropilin-2 expression in breast cancer: correlation with lymph node metastasis, poor prognosis, and regulation of CXCR4 expression. BMC Cancer 9(1):220. https:\/\/doi.org\/10.1186\/1471-2407-9-220\/FIGURES\/4","journal-title":"BMC Cancer"},{"issue":"6","key":"10289_CR39","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1016\/J.APSB.2021.02.008","volume":"11","author":"H Zhang","year":"2021","unstructured":"Zhang H, Fu L (2021) The role of ALDH2 in tumorigenesis and tumor progression: Targeting ALDH2 as a potential cancer treatment. Acta Pharm Sin B 11(6):1400. https:\/\/doi.org\/10.1016\/J.APSB.2021.02.008","journal-title":"Acta Pharm Sin B"},{"issue":"3","key":"10289_CR40","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1093\/NAR\/GKX1190","volume":"46","author":"A Sundqvist","year":"2018","unstructured":"Sundqvist A et al (2018) JUNB governs a feed-forward network of TGF\u03b2 signaling that aggravates breast cancer invasion. Nucleic Acids Res 46(3):1180. https:\/\/doi.org\/10.1093\/NAR\/GKX1190","journal-title":"Nucleic Acids Res"},{"issue":"10","key":"10289_CR41","doi-asserted-by":"publisher","first-page":"7804","DOI":"10.18632\/ONCOTARGET.3158","volume":"6","author":"Y Qiao","year":"2015","unstructured":"Qiao Y et al (2015) AP-1-mediated chromatin looping regulates ZEB2 transcription: new insights into TNF\u03b1-induced epithelial-mesenchymal transition in triple-negative breast cancer. Oncotarget 6(10):7804\u20137814. https:\/\/doi.org\/10.18632\/ONCOTARGET.3158","journal-title":"Oncotarget"},{"issue":"1","key":"10289_CR42","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/1476-4598-12-28","volume":"12","author":"N Ludyga","year":"2013","unstructured":"Ludyga N et al (2013) The impact of cysteine-rich intestinal protein 1 (CRIP1) in human breast cancer. Mol Cancer 12(1):28. https:\/\/doi.org\/10.1186\/1476-4598-12-28","journal-title":"Mol Cancer"},{"issue":"13","key":"10289_CR43","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.1038\/SJ.ONC.1206199","volume":"22","author":"SL Kominsky","year":"2003","unstructured":"Kominsky SL et al (2003) Loss of the tight junction protein claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast. Oncogene 22(13):2021\u20132033. https:\/\/doi.org\/10.1038\/SJ.ONC.1206199","journal-title":"Oncogene"},{"issue":"4","key":"10289_CR44","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1016\/J.BBAMEM.2008.11.005","volume":"1788","author":"TA Martin","year":"2009","unstructured":"Martin TA, Jiang WG (2009) Loss of tight junction barrier function and its role in cancer metastasis. Biochim Biophys Acta (BBA)\u2014Biomembranes 1788(4):872\u2013891. https:\/\/doi.org\/10.1016\/J.BBAMEM.2008.11.005","journal-title":"Biochim Biophys Acta (BBA)\u2014Biomembranes"},{"issue":"17","key":"10289_CR45","doi-asserted-by":"publisher","first-page":"24677","DOI":"10.18632\/ONCOTARGET.8250","volume":"7","author":"K-A Hyun","year":"2016","unstructured":"Hyun K-A et al (2016) Epithelial-to-mesenchymal transition leads to loss of EpCAM and different physical properties in circulating tumor cells from metastatic breast cancer. Oncotarget 7(17):24677. https:\/\/doi.org\/10.18632\/ONCOTARGET.8250","journal-title":"Oncotarget"},{"issue":"6","key":"10289_CR46","doi-asserted-by":"publisher","first-page":"4869","DOI":"10.3892\/OL.2016.5369","volume":"12","author":"F Liu","year":"2016","unstructured":"Liu F, Gu LN, Shan BE, Geng CZ, Sang MX (2016) Biomarkers for EMT and MET in breast cancer: an update. Oncol Lett 12(6):4869. https:\/\/doi.org\/10.3892\/OL.2016.5369","journal-title":"Oncol Lett"},{"issue":"6","key":"10289_CR47","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1172\/JCI39104","volume":"119","author":"R Kalluri","year":"2009","unstructured":"Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119(6):1420. https:\/\/doi.org\/10.1172\/JCI39104","journal-title":"J Clin Invest"},{"issue":"3","key":"10289_CR48","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1200\/JCO.20.3.719","volume":"20","author":"CL Vogel","year":"2002","unstructured":"Vogel CL et al (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20(3):719\u2013726. https:\/\/doi.org\/10.1200\/JCO.20.3.719","journal-title":"J Clin Oncol"},{"issue":"6","key":"10289_CR49","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1007\/S10585-011-9388-6\/FIGURES\/7","volume":"28","author":"ET Roussos","year":"2011","unstructured":"Roussos ET et al (2011) Mena invasive (MenaINV) and Mena11a isoforms play distinct roles in breast cancer cell cohesion and association with TMEM. Clin Exp Metastasis 28(6):515\u2013527. https:\/\/doi.org\/10.1007\/S10585-011-9388-6\/FIGURES\/7","journal-title":"Clin Exp Metastasis"},{"issue":"6","key":"10289_CR50","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/J.DEVCEL.2008.09.003","volume":"15","author":"U Philippar","year":"2008","unstructured":"Philippar U et al (2008) A mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis. Dev Cell 15(6):813. https:\/\/doi.org\/10.1016\/J.DEVCEL.2008.09.003","journal-title":"Dev Cell"},{"issue":"1","key":"10289_CR51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-021-27308-2","volume":"12","author":"VP Sharma","year":"2021","unstructured":"Sharma VP et al (2021) Live tumor imaging shows macrophage\u00a0induction and TMEM-mediated enrichment of cancer stem cells during metastatic dissemination. Nat Commun 12(1):1\u201324. https:\/\/doi.org\/10.1038\/s41467-021-27308-2","journal-title":"Nat Commun"},{"issue":"1","key":"10289_CR52","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-022-28076-3","volume":"13","author":"L Borriello","year":"2022","unstructured":"Borriello L et al (2022) Primary tumor associated macrophages activate programs of invasion and dormancy in disseminating tumor cells. Nat Commun 13(1):1\u201319. https:\/\/doi.org\/10.1038\/s41467-022-28076-3","journal-title":"Nat Commun"},{"issue":"9","key":"10289_CR53","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1242\/JCS.183129\/-\/DC2","volume":"129","author":"GS Karagiannis","year":"2016","unstructured":"Karagiannis GS, Goswami S, Jones JG, Oktay MH, Condeelis JS (2016) Signatures of breast cancer metastasis at a glance. J Cell Sci 129(9):1751\u20131758. https:\/\/doi.org\/10.1242\/JCS.183129\/-\/DC2","journal-title":"J Cell Sci"},{"issue":"397","key":"10289_CR54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/SCITRANSLMED.AAN0026","volume":"9","author":"GS Karagiannis","year":"2017","unstructured":"Karagiannis GS et al (2017) Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism. Sci Transl Med 9(397):1\u201315. https:\/\/doi.org\/10.1126\/SCITRANSLMED.AAN0026","journal-title":"Sci Transl Med"},{"issue":"11","key":"10289_CR55","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1158\/1078-0432.CCR-17-3070","volume":"24","author":"TM Ashton","year":"2018","unstructured":"Ashton TM, Gillies McKenna W, Kunz-Schughart LA, Higgins GS (2018) Oxidative phosphorylation as an emerging target in cancer therapy. Clin Cancer Res 24(11):2482\u20132490. https:\/\/doi.org\/10.1158\/1078-0432.CCR-17-3070","journal-title":"Clin Cancer Res"},{"key":"10289_CR56","doi-asserted-by":"publisher","DOI":"10.1038\/NCOMMS13041","volume":"7","author":"E Gaude","year":"2016","unstructured":"Gaude E, Frezza C (2016) Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival. Nat Commun 7:13041. https:\/\/doi.org\/10.1038\/NCOMMS13041","journal-title":"Nat Commun"},{"issue":"1","key":"10289_CR57","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41392-020-0134-x","volume":"5","author":"J Fares","year":"2020","unstructured":"Fares J, Fares MY, Khachfe HH, Salhab HA, Fares Y (2020) Molecular principles of metastasis: a hallmark of cancer revisited. Sig Transduct Target Ther 5(1):1\u201317. https:\/\/doi.org\/10.1038\/s41392-020-0134-x","journal-title":"Sig Transduct Target Ther"},{"issue":"2","key":"10289_CR58","doi-asserted-by":"publisher","first-page":"200","DOI":"10.3390\/PATHOPHYSIOLOGY29020017","volume":"29","author":"AK Pal","year":"2022","unstructured":"Pal AK et al (2022) Metabolomics and EMT markers of breast cancer a crosstalk and future perspective. Pathophysiology 29(2):200\u2013222. https:\/\/doi.org\/10.3390\/PATHOPHYSIOLOGY29020017","journal-title":"Pathophysiology"},{"issue":"4","key":"10289_CR59","doi-asserted-by":"publisher","first-page":"365","DOI":"10.4161\/CAM.21326","volume":"6","author":"GF Le Bras","year":"2012","unstructured":"Le Bras GF, Taubenslag KJ, Andl CD (2012) The regulation of cell-cell adhesion during epithelial-mesenchymal transition, motility and tumor progression. Cell Adh Migr 6(4):365. https:\/\/doi.org\/10.4161\/CAM.21326","journal-title":"Cell Adh Migr"},{"issue":"2","key":"10289_CR60","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/S10585-008-9225-8","volume":"26","author":"S Goswami","year":"2009","unstructured":"Goswami S et al (2009) Identification of invasion specific splice variants of the cytoskeletal protein Mena present in mammary tumor cells during invasion in vivo. Clin Exp Metastasis 26(2):153. https:\/\/doi.org\/10.1007\/S10585-008-9225-8","journal-title":"Clin Exp Metastasis"},{"issue":"13","key":"10289_CR61","doi-asserted-by":"publisher","first-page":"2120","DOI":"10.1242\/JCS.086231","volume":"124","author":"ET Roussos","year":"2011","unstructured":"Roussos ET et al (2011) Mena invasive (MenaINV) promotes multicellular streaming motility and transendothelial migration in a mouse model of breast cancer. J Cell Sci 124(13):2120. https:\/\/doi.org\/10.1242\/JCS.086231","journal-title":"J Cell Sci"},{"issue":"7","key":"10289_CR62","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1158\/1078-0432.CCR-08-2179","volume":"15","author":"BD Robinson","year":"2009","unstructured":"Robinson BD et al (2009) Tumor microenvironment of metastasis in human breast carcinoma: a potential prognostic marker linked to hematogenous dissemination. Clin Cancer Res 15(7):2433. https:\/\/doi.org\/10.1158\/1078-0432.CCR-08-2179","journal-title":"Clin Cancer Res"},{"issue":"17","key":"10289_CR63","doi-asserted-by":"publisher","first-page":"5187","DOI":"10.1158\/1078-0432.CCR-17-0741","volume":"23","author":"A Orillion","year":"2017","unstructured":"Orillion A et al (2017) Entinostat neutralizes myeloid-derived suppressor cells and enhances the antitumor effect of PD-1 inhibition in murine models of lung and renal cell carcinoma. Clin Cancer Res 23(17):5187\u20135201. https:\/\/doi.org\/10.1158\/1078-0432.CCR-17-0741","journal-title":"Clin Cancer Res"},{"issue":"32","key":"10289_CR64","doi-asserted-by":"publisher","first-page":"11774","DOI":"10.1073\/PNAS.1410626111\/-\/DCSUPPLEMENTAL","volume":"111","author":"K Kim","year":"2014","unstructured":"Kim K et al (2014) Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells. Proc Natl Acad Sci USA 111(32):11774\u201311779. https:\/\/doi.org\/10.1073\/PNAS.1410626111\/-\/DCSUPPLEMENTAL","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Clinical &amp; Experimental Metastasis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10585-024-10289-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10585-024-10289-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10585-024-10289-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T06:17:24Z","timestamp":1732256244000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10585-024-10289-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,8]]},"references-count":64,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10289"],"URL":"https:\/\/doi.org\/10.1007\/s10585-024-10289-z","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.01.25.577282","asserted-by":"object"}]},"ISSN":["0262-0898","1573-7276"],"issn-type":[{"value":"0262-0898","type":"print"},{"value":"1573-7276","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,8]]},"assertion":[{"value":"11 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"EMJ is a paid consultant for Adaptive Biotech, CSTONE, Achilles, DragonFly, and Genocea. She receives funding from Lustgarten Foundation and Bristol Myer Squibb. She is the Chief Medical Advisor for Lustgarten and SAB advisor to the Parker Institute for Cancer Immunotherapy (PICI) and for the C3 Cancer Institute.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All animal studies were approved by the Institutional Review Board of USC and Johns Hopkins University.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}