{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:14:16Z","timestamp":1789683256169,"version":"4.0.1"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No.8210114078"],"award-info":[{"award-number":["No.8210114078"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sine oculis homeobox homolog 1 (SIX1) is a transcription factor that has recently been identified as a crucial regulator of embryonic development and tumorigenesis. SIX1 is upregulated in different types of tumors, including breast cancer. However, the role and mechanism of SIX1 upregulation in breast cancer carcinogenesis remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we utilized various databases such as UALCAN, TCGA, STRING, and Kaplan\u2013Meier Plotter to investigate the mRNA expression, prognosis, transcriptional profile changes, signal pathway rewiring, and interaction with cancer stem cells of SIX1 in breast cancer. We also conducted both in vitro and in vivo experiments to validate its positive regulation effect on breast cancer stem cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings demonstrated that the expression of SIX1 varies among different subtypes of breast cancer and that it upregulates breast cancer grading and lymph node metastasis. Besides, SIX1 participates in the rewiring of several cancer signaling pathways, including estrogen, WNT, MAPK, and other pathways, and interacts with cancer stem cells. SIX1 showed a significant positive correlation with breast cancer stem cell markers such as ALDH1A1, EPCAM, ITGB1, and SOX2. Moreover, our in vitro and in vivo experiments confirmed that SIX1 can promote the increase in the proportion of stem cells and tumor progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Altogether, our results suggest that SIX1 plays an essential regulatory role in breast cancer's occurrence, and its amplification can be utilized as a diagnostic and prognostic predictor. The interaction between SIX1 and cancer stem cells may play a critical role in regulating breast cancer's initiation and metastasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-023-04679-2","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T01:01:32Z","timestamp":1701219692000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["SIX1 amplification modulates stemness and tumorigenesis in breast cancer"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2617-8651","authenticated-orcid":false,"given":"Liantao","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faminzi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanqing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deguang","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengrong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,29]]},"reference":[{"issue":"6","key":"4679_CR1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca-a Cancer J Clin. 2018;68(6):394\u2013424. https:\/\/doi.org\/10.3322\/caac.21492.","journal-title":"Ca-a Cancer J Clin"},{"issue":"1","key":"4679_CR2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21654","volume":"71","author":"RL Siegel","year":"2021","unstructured":"Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7\u201333. https:\/\/doi.org\/10.3322\/caac.21654.","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"4679_CR3","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s40364-021-00310-y","volume":"9","author":"M Yi","year":"2021","unstructured":"Yi M, Li T, Niu M, Luo S, Chu Q, Wu K. Epidemiological trends of women\u2019s cancers from 1990 to 2019 at the global, regional, and national levels: a population-based study. Biomark Res. 2021;9(1):55. https:\/\/doi.org\/10.1186\/s40364-021-00310-y.","journal-title":"Biomark Res"},{"issue":"5","key":"4679_CR4","doi-asserted-by":"publisher","first-page":"409","DOI":"10.3322\/caac.21731","volume":"72","author":"KD Miller","year":"2022","unstructured":"Miller KD, Nogueira L, Devasia T, Mariotto AB, Yabroff KR, Jemal A, Kramer J, Siegel RL. Cancer treatment and survivorship statistics, 2022. CA Cancer J Clin. 2022;72(5):409\u201336. https:\/\/doi.org\/10.3322\/caac.21731.","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"4679_CR5","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40164-022-00363-1","volume":"12","author":"L Guo","year":"2023","unstructured":"Guo L, Kong D, Liu J, Zhan L, Luo L, Zheng W, Zheng Q, Chen C, Sun S. Breast cancer heterogeneity and its implication in personalized precision therapy. Exp Hematol Oncol. 2023;12(1):3. https:\/\/doi.org\/10.1186\/s40164-022-00363-1.","journal-title":"Exp Hematol Oncol"},{"issue":"4","key":"4679_CR6","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/0092-8674(88)90209-7","volume":"55","author":"M Levine","year":"1988","unstructured":"Levine M, Hoey T. Homeobox proteins as sequence-specific transcription factors. Cell. 1988;55(4):537\u201340. https:\/\/doi.org\/10.1016\/0092-8674(88)90209-7.","journal-title":"Cell"},{"issue":"1-2","key":"4679_CR7","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/s0925-4773(99)00045-3","volume":"83","author":"HC Seo","year":"1999","unstructured":"Seo HC, Curtiss J, Mlodzik M, Fjose A. Six class homeobox genes in drosophila belong to three distinct families and are involved in head development. Mech Dev. 1999;83(1\u20132):127\u201339. https:\/\/doi.org\/10.1016\/s0925-4773(99)00045-3.","journal-title":"Mech Dev"},{"issue":"10","key":"4679_CR8","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/0168-9525(90)90253-3","volume":"6","author":"WJ Gehring","year":"1990","unstructured":"Gehring WJ, M\u00fcller M, Affolter M, Percival-Smith A, Billeter M, Qian YQ, Otting G, W\u00fcthrich K. The structure of the homeodomain and its functional implications. Trends Genet. 1990;6(10):323\u20139. https:\/\/doi.org\/10.1016\/0168-9525(90)90253-3.","journal-title":"Trends Genet"},{"issue":"4","key":"4679_CR9","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1007\/s00018-008-8335-4","volume":"66","author":"JP Kumar","year":"2009","unstructured":"Kumar JP. The sine oculis homeobox (SIX) family of transcription factors as regulators of development and disease. Cell Mol Life Sci. 2009;66(4):565\u201383. https:\/\/doi.org\/10.1007\/s00018-008-8335-4.","journal-title":"Cell Mol Life Sci"},{"issue":"Pt B","key":"4679_CR10","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.ijbiomac.2021.10.133","volume":"193","author":"A Rafiq","year":"2021","unstructured":"Rafiq A, Aashaq S, Jan I, Beigh MA. SIX1 transcription factor: a review of cellular functions and regulatory dynamics. Int J Biol Macromol. 2021;193(Pt B):1151\u201364. https:\/\/doi.org\/10.1016\/j.ijbiomac.2021.10.133.","journal-title":"Int J Biol Macromol"},{"issue":"19","key":"4679_CR11","doi-asserted-by":"publisher","first-page":"5597","DOI":"10.1158\/0008-5472.Can-13-3598","volume":"74","author":"D Liu","year":"2014","unstructured":"Liu D, Li L, Zhang XX, Wan DY, Xi BX, Hu Z, Ding WC, Zhu D, Wang XL, Wang W, Feng ZH. SIX1 promotes tumor lymphangiogenesis by coordinating TGF\u03b2 signals that increase expression of VEGF-C. Cancer Res. 2014;74(19):5597\u2013607. https:\/\/doi.org\/10.1158\/0008-5472.Can-13-3598.","journal-title":"Cancer Res"},{"issue":"4","key":"4679_CR12","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/nsmb.2505","volume":"20","author":"AN Patrick","year":"2013","unstructured":"Patrick AN, Cabrera JH, Smith AL, Chen XS, Ford HL, Zhao R. Structure-function analyses of the human SIX1-EYA2 complex reveal insights into metastasis and BOR syndrome. Nat Struct Mol Biol. 2013;20(4):447\u201353. https:\/\/doi.org\/10.1038\/nsmb.2505.","journal-title":"Nat Struct Mol Biol"},{"issue":"1","key":"4679_CR13","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s12964-023-01160-x","volume":"21","author":"M Fan","year":"2023","unstructured":"Fan M, Shi Y, Zhao J, Li L. Cancer stem cell fate determination: mito-nuclear communication. Cell Commun Signal. 2023;21(1):159. 2019;9:1450. https:\/\/doi.org\/10.1186\/s12964-023-01160-x.","journal-title":"Cell Commun Signal"},{"issue":"3","key":"4679_CR14","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/nm.2304","volume":"17","author":"H Clevers","year":"2011","unstructured":"Clevers H. The cancer stem cell: premises, promises and challenges. Nat Med. 2011;17(3):313\u20139. https:\/\/doi.org\/10.1038\/nm.2304.","journal-title":"Nat Med"},{"issue":"7","key":"4679_CR15","doi-asserted-by":"publisher","first-page":"3983","DOI":"10.1073\/pnas.0530291100","volume":"100","author":"M Al-Hajj","year":"2003","unstructured":"Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100(7):3983\u20138. https:\/\/doi.org\/10.1073\/pnas.0530291100.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"5","key":"4679_CR16","doi-asserted-by":"publisher","first-page":"101025","DOI":"10.1016\/j.xcrm.2023.101025","volume":"4","author":"T Ranjan","year":"2023","unstructured":"Ranjan T, Sengupta S, Glantz MJ, Green RM, Yu A, Aregawi D, Chaudhary R, Chen R, Zuccarello M, Lu-Emerson C, Moulding HD. Cancer stem cell assay-guided chemotherapy improves survival of patients with recurrent glioblastoma in a randomized trial. Cell Rep Med. 2023;4(5):101025. https:\/\/doi.org\/10.1016\/j.xcrm.2023.101025.","journal-title":"Cell Rep Med"},{"issue":"4","key":"4679_CR17","doi-asserted-by":"publisher","first-page":"R100","DOI":"10.1186\/bcr3219","volume":"14","author":"R Iwanaga","year":"2012","unstructured":"Iwanaga R, Wang CA, Micalizzi DS, Harrell JC, Jedlicka P, Sartorius CA, Kabos P, Farabaugh SM, Bradford AP, Ford HL. Expression of Six1 in luminal breast cancers predicts poor prognosis and promotes increases in tumor initiating cells by activation of extracellular signal-regulated kinase and transforming growth factor-beta signaling pathways. Breast Cancer Res. 2012;14(4):R100. https:\/\/doi.org\/10.1186\/bcr3219.","journal-title":"Breast Cancer Res"},{"issue":"3","key":"4679_CR18","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1093\/carcin\/bgw121","volume":"38","author":"H Xu","year":"2017","unstructured":"Xu H, Zhang Y, Pe\u00f1a MM, Pirisi L, Creek KE. Six1 promotes colorectal cancer growth and metastasis by stimulating angiogenesis and recruiting tumor-associated macrophages. Carcinogenesis. 2017;38(3):281\u201392. https:\/\/doi.org\/10.1093\/carcin\/bgw121.","journal-title":"Carcinogenesis"},{"issue":"2","key":"4679_CR19","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1111\/cas.13135","volume":"108","author":"T Nishimura","year":"2017","unstructured":"Nishimura T, Tamaoki M, Komatsuzaki R, Oue N, Taniguchi H, Komatsu M, Aoyagi K, Minashi K, Chiwaki F, Shinohara H, Tachimori Y. SIX1 maintains tumor basal cells via transforming growth factor-\u03b2 pathway and associates with poor prognosis in esophageal cancer. Cancer Sci. 2017;108(2):216\u201325. https:\/\/doi.org\/10.1111\/cas.13135.","journal-title":"Cancer Sci"},{"issue":"1","key":"4679_CR20","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1186\/s12885-017-3225-5","volume":"17","author":"T Lerbs","year":"2017","unstructured":"Lerbs T, Bisht S, Sch\u00f6lch S, Pecqueux M, Kristiansen G, Schneider M, Hofmann BT, Welsch T, Reissfelder C, Rahbari NN, Fritzmann J. Inhibition of Six1 affects tumour invasion and the expression of cancer stem cell markers in pancreatic cancer. BMC Cancer. 2017;17(1):249. https:\/\/doi.org\/10.1186\/s12885-017-3225-5.","journal-title":"BMC Cancer"},{"issue":"1","key":"4679_CR21","doi-asserted-by":"publisher","first-page":"9227","DOI":"10.1038\/s41598-018-27521-y","volume":"8","author":"\u00c1 Nagy","year":"2018","unstructured":"Nagy \u00c1, L\u00e1nczky A, Menyh\u00e1rt O, Gy\u0151rffy B. Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep. 2018;8(1):9227. https:\/\/doi.org\/10.1038\/s41598-018-27521-y.","journal-title":"Sci Rep"},{"issue":"8","key":"4679_CR22","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.neo.2017.05.002","volume":"19","author":"DS Chandrashekar","year":"2017","unstructured":"Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi B, Varambally S. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017;19(8):649\u201358. https:\/\/doi.org\/10.1016\/j.neo.2017.05.002.","journal-title":"Neoplasia"},{"issue":"4","key":"4679_CR23","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.immuni.2018.03.023","volume":"48","author":"V Thorsson","year":"2018","unstructured":"Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH. The Immune Landscape of Cancer. Immunity. 2018;48(4):812-830.e814. https:\/\/doi.org\/10.1016\/j.immuni.2018.03.023.","journal-title":"Immunity"},{"key":"4679_CR24","doi-asserted-by":"publisher","first-page":"2612","DOI":"10.1038\/ncomms3612","volume":"4","author":"K Yoshihara","year":"2013","unstructured":"Yoshihara K, Shahmoradgoli M, Mart\u00ednez E, Vegesna R, Kim H, Torres-Garcia W, Trevi\u00f1o V, Shen H, Laird PW, Levine DA, Carter SL. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4:2612. https:\/\/doi.org\/10.1038\/ncomms3612.","journal-title":"Nat Commun"},{"issue":"5","key":"4679_CR25","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1158\/2159-8290.Cd-12-0095","volume":"2","author":"E Cerami","year":"2012","unstructured":"Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2(5):401\u20134. https:\/\/doi.org\/10.1158\/2159-8290.Cd-12-0095.","journal-title":"Cancer Discov"},{"issue":"D1","key":"4679_CR26","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","volume":"51","author":"D Szklarczyk","year":"2023","unstructured":"Szklarczyk D, Kirsch R, Koutrouli M, Nastou K, Mehryary F, Hachilif R, Gable AL, Fang T, Doncheva NT, Pyysalo S, Bork P. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 2023;51(D1):D638\u2013d646. https:\/\/doi.org\/10.1093\/nar\/gkac1000.","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"4679_CR27","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/j.cell.2018.03.034","volume":"173","author":"TM Malta","year":"2018","unstructured":"Malta TM, Sokolov A, Gentles AJ, Burzykowski T, Poisson L, Weinstein JN, Kami\u0144ska B, Huelsken J, Omberg L, Gevaert O, Colaprico A. Machine learning identifies stemness features associated with oncogenic dedifferentiation. Cell. 2018;173(2):338\u2013354.e315. https:\/\/doi.org\/10.1016\/j.cell.2018.03.034.","journal-title":"Cell"},{"key":"4679_CR28","doi-asserted-by":"publisher","first-page":"15773","DOI":"10.1038\/ncomms15773","volume":"8","author":"D Neelakantan","year":"2017","unstructured":"Neelakantan D, Zhou H, Oliphant MU, Zhang X, Simon LM, Henke DM, Shaw CA, Wu MF, Hilsenbeck SG, White LD, Lewis MT. EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells. Nat Commun. 2017;8:15773. https:\/\/doi.org\/10.1038\/ncomms15773.","journal-title":"Nat Commun"},{"issue":"47","key":"4679_CR29","doi-asserted-by":"publisher","first-page":"5477","DOI":"10.1038\/onc.2013.516","volume":"33","author":"A Vassilopoulos","year":"2014","unstructured":"Vassilopoulos A, Chisholm C, Lahusen T, Zheng H, Deng CX. A critical role of CD29 and CD49f in mediating metastasis for cancer-initiating cells isolated from a Brca1-associated mouse model of breast cancer. Oncogene. 2014;33(47):5477\u201382. https:\/\/doi.org\/10.1038\/onc.2013.516.","journal-title":"Oncogene"},{"key":"4679_CR30","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.semcancer.2021.03.008","volume":"82","author":"R Zhang","year":"2022","unstructured":"Zhang R, Tu J, Liu S. Novel molecular regulators of breast cancer stem cell plasticity and heterogeneity. Semin Cancer Biol. 2022;82:11\u201325. https:\/\/doi.org\/10.1016\/j.semcancer.2021.03.008.","journal-title":"Semin Cancer Biol"},{"issue":"5","key":"4679_CR31","doi-asserted-by":"publisher","first-page":"375","DOI":"10.2174\/1574888x13666180810120012","volume":"14","author":"ME Toledo-Guzm\u00e1n","year":"2019","unstructured":"Toledo-Guzm\u00e1n ME, Hern\u00e1ndez MI, G\u00f3mez-Gallegos \u00c1A, Ortiz-S\u00e1nchez E. ALDH as a stem cell marker in solid tumors. Curr Stem Cell Res Ther. 2019;14(5):375\u201388. https:\/\/doi.org\/10.2174\/1574888x13666180810120012.","journal-title":"Curr Stem Cell Res Ther"},{"issue":"7015","key":"4679_CR32","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/nature03099","volume":"432","author":"H Rajagopalan","year":"2004","unstructured":"Rajagopalan H, Lengauer C. Aneuploidy and cancer. Nature. 2004;432(7015):338\u201341. https:\/\/doi.org\/10.1038\/nature03099.","journal-title":"Nature"},{"issue":"7832","key":"4679_CR33","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1038\/s41586-020-2698-6","volume":"587","author":"TB Watkins","year":"2020","unstructured":"Watkins TB, Lim EL, Petkovic M, Elizalde S, Birkbak NJ, Wilson GA, Moore DA, Gr\u00f6nroos E, Rowan A, Dewhurst SM, Demeulemeester J. Pervasive chromosomal instability and karyotype order in tumour evolution. Nature. 2020;587(7832):126\u201332. https:\/\/doi.org\/10.1038\/s41586-020-2698-6.","journal-title":"Nature"},{"issue":"5","key":"4679_CR34","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1172\/jci59858","volume":"122","author":"CA Wang","year":"2012","unstructured":"Wang CA, Jedlicka P, Patrick AN, Micalizzi DS, Lemmer KC, Deitsch E, Cas\u00e1s-Selves M, Harrell JC, Ford HL. SIX1 induces lymphangiogenesis and metastasis via upregulation of VEGF-C in mouse models of breast cancer. J Clin Invest. 2012;122(5):1895\u2013906. https:\/\/doi.org\/10.1172\/jci59858.","journal-title":"J Clin Invest"},{"issue":"2","key":"4679_CR35","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1517\/14728222.2014.978860","volume":"19","author":"MA Blevins","year":"2015","unstructured":"Blevins MA, Towers CG, Patrick AN, Zhao R, Ford HL. The SIX1-EYA transcriptional complex as a therapeutic target in cancer. Expert Opin Ther Targets. 2015;19(2):213\u201325. https:\/\/doi.org\/10.1517\/14728222.2014.978860.","journal-title":"Expert Opin Ther Targets"},{"issue":"6964","key":"4679_CR36","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/nature02083","volume":"426","author":"X Li","year":"2003","unstructured":"Li X, Oghi KA, Zhang J, Krones A, Bush KT, Glass CK, Nigam SK, Aggarwal AK, Maas R, Rose DW, Rosenfeld MG. Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature. 2003;426(6964):247\u201354. https:\/\/doi.org\/10.1038\/nature02083.","journal-title":"Nature"},{"issue":"9","key":"4679_CR37","doi-asserted-by":"publisher","first-page":"2663","DOI":"10.1172\/jci37691","volume":"119","author":"EL McCoy","year":"2009","unstructured":"McCoy EL, Iwanaga R, Jedlicka P, Abbey NS, Chodosh LA, Heichman KA, Welm AL, Ford HL. Six1 expands the mouse mammary epithelial stem\/progenitor cell pool and induces mammary tumors that undergo epithelial-mesenchymal transition. J Clin Invest. 2009;119(9):2663\u201377. https:\/\/doi.org\/10.1172\/jci37691.","journal-title":"J Clin Invest"},{"issue":"1","key":"4679_CR38","doi-asserted-by":"publisher","first-page":"17010","DOI":"10.1038\/celldisc.2017.10","volume":"3","author":"P Shi","year":"2017","unstructured":"Shi P, Liu W, Tala, Wang H, Li F, Zhang H, Wu Y, Kong Y, Zhou Z, Wang C, Chen W, Liu R. Metformin suppresses triple-negative breast cancer stem cells by targeting KLF5 for degradation. Cell Discov. 2017;3(1):17010. https:\/\/doi.org\/10.1038\/celldisc.2017.10.","journal-title":"Cell Discov"},{"issue":"1","key":"4679_CR39","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s13045-021-01194-z","volume":"14","author":"S Liu","year":"2021","unstructured":"Liu S, Sun Y, Hou Y, Yang L, Wan X, Qin Y, Liu Y, Wang R, Zhu P, Teng Y, Liu M. A novel lncRNA ROPM-mediated lipid metabolism governs breast cancer stem cell properties. J Hematol Oncol. 2021;14(1):178. https:\/\/doi.org\/10.1186\/s13045-021-01194-z.","journal-title":"J Hematol Oncol"},{"issue":"4","key":"4679_CR40","doi-asserted-by":"publisher","first-page":"165432","DOI":"10.1016\/j.bbadis.2019.03.005","volume":"1866","author":"IS Mohiuddin","year":"2020","unstructured":"Mohiuddin IS, Wei SJ, Kang MH. Role of OCT4 in cancer stem-like cells and chemotherapy resistance. Biochim Biophys Acta Mol Basis Dis. 2020;1866(4): 165432. https:\/\/doi.org\/10.1016\/j.bbadis.2019.03.005.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"5","key":"4679_CR41","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1038\/s41419-021-03733-5","volume":"12","author":"Y Zhu","year":"2021","unstructured":"Zhu Y, Huang S, Chen S, Chen J, Wang Z, Wang Y, Zheng H. SOX2 promotes chemoresistance, cancer stem cells properties, and epithelial-mesenchymal transition by \u03b2-catenin and Beclin1\/autophagy signaling in colorectal cancer. Cell Death Dis. 2021;12(5):449. https:\/\/doi.org\/10.1038\/s41419-021-03733-5.","journal-title":"Cell Death Dis"},{"issue":"23","key":"4679_CR42","doi-asserted-by":"publisher","first-page":"5919","DOI":"10.1158\/0008-5472.Can-21-1337","volume":"81","author":"C Liu","year":"2021","unstructured":"Liu C, Qiang J, Deng Q, Xia J, Deng L, Zhou L, Wang D, He X, Liu Y, Zhao B, Lv J. ALDH1A1 Activity in Tumor-Initiating Cells Remodels Myeloid-Derived Suppressor Cells to Promote Breast Cancer Progression. Cancer Res. 2021;81(23):5919\u201334. https:\/\/doi.org\/10.1158\/0008-5472.Can-21-1337.","journal-title":"Cancer Res"},{"issue":"4","key":"4679_CR43","doi-asserted-by":"publisher","first-page":"3626","DOI":"10.1002\/jcp.29252","volume":"235","author":"D Zhang","year":"2020","unstructured":"Zhang D, Yang L, Liu X, Gao J, Liu T, Yan Q, Yang X. Hypoxia modulates stem cell properties and induces EMT through N-glycosylation of EpCAM in breast cancer cells. J Cell Physiol. 2020;235(4):3626\u201333. https:\/\/doi.org\/10.1002\/jcp.29252.","journal-title":"J Cell Physiol"},{"issue":"3","key":"4679_CR44","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1002\/ijc.32183","volume":"145","author":"R Barnawi","year":"2019","unstructured":"Barnawi R, Al-Khaldi S, Colak D, Tulbah A, Al-Tweigeri T, Fallatah M, Monies D, Ghebeh H, Al-Alwan M. \u03b21 Integrin is essential for fascin-mediated breast cancer stem cell function and disease progression. Int J Cancer. 2019;145(3):830\u201341. https:\/\/doi.org\/10.1002\/ijc.32183.","journal-title":"Int J Cancer"},{"key":"4679_CR45","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.3389\/fonc.2019.01450","volume":"9","author":"D Kong","year":"2019","unstructured":"Kong D, Li A, Liu Y, Cui Q, Wang K, Zhang D, Tang J, Du Y, Liu Z, Wu G, Wu K. SIX1 activates STAT3 signaling to promote the proliferation of thyroid carcinoma via EYA1. Front Oncol. 2019;9:1450. https:\/\/doi.org\/10.3389\/fonc.2019.01450.","journal-title":"Front Oncol"},{"key":"4679_CR46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.acr.2018.12.001","volume":"141","author":"TJ Kingsbury","year":"2019","unstructured":"Kingsbury TJ, Kim M, Civin CI. Regulation of cancer stem cell properties by SIX1, a member of the PAX-SIX-EYA-DACH network. Adv Cancer Res. 2019;141:1\u201342. https:\/\/doi.org\/10.1002\/jcp.29252.","journal-title":"Adv Cancer Res"},{"issue":"8","key":"4679_CR47","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.1002\/stem.2406%JStemCells","volume":"34","author":"R Sato","year":"2016","unstructured":"Sato R, Semba T, Saya H, Arima Y. Concise review: stem cells and epithelial-mesenchymal transition in cancer: biological implications and therapeutic targets. Stem Cells. 2016;34(8):1997\u20132007. https:\/\/doi.org\/10.1002\/stem.2406%JStemCells.","journal-title":"Stem Cells"},{"issue":"9","key":"4679_CR48","doi-asserted-by":"publisher","first-page":"2678","DOI":"10.1172\/jci37815","volume":"119","author":"DS Micalizzi","year":"2009","unstructured":"Micalizzi DS, Christensen KL, Jedlicka P, Coletta RD, Bar\u00f3n AE, Harrell JC, Horwitz KB, Billheimer D, Heichman KA, Welm AL, Schiemann WP. The Six1 homeoprotein induces human mammary carcinoma cells to undergo epithelial-mesenchymal transition and metastasis in mice through increasing TGF-beta signaling. J Clin Invest. 2009;119(9):2678\u201390. https:\/\/doi.org\/10.1172\/jci37815.","journal-title":"J Clin Invest"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-023-04679-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-023-04679-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-023-04679-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T01:03:41Z","timestamp":1701219821000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-023-04679-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,29]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["4679"],"URL":"https:\/\/doi.org\/10.1186\/s12967-023-04679-2","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,29]]},"assertion":[{"value":"23 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal experiment of the study was approved by the Laboratory Animal Welfare & Ethics Committee of Renmin Hospital at Wuhan University (Issue No. 20200702).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The author (s) declare no potential conficts of interest with respect to the research, authorship, and\/or publication of this article.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"866"}}