{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T08:55:54Z","timestamp":1790326554496,"version":"4.1.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T00:00:00Z","timestamp":1548028800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672543"],"award-info":[{"award-number":["81672543"]}],"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":["31401233"],"award-info":[{"award-number":["31401233"]}],"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":["81630073"],"award-info":[{"award-number":["81630073"]}],"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":["81872406"],"award-info":[{"award-number":["81872406"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"crossref","award":["2017YFA0102900"],"award-info":[{"award-number":["2017YFA0102900"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"crossref","award":["16JC1405700"],"award-info":[{"award-number":["16JC1405700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"crossref"}]},{"name":"High Peak IV subject on stem cells and translational medicine from Education Commission of Shanghai Municipality"},{"name":"KC Wong foundation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Exp Clin Cancer Res"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s13046-019-1025-2","type":"journal-article","created":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T14:02:51Z","timestamp":1548079371000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Elevated expression of Gab1 promotes breast cancer metastasis by dissociating the PAR complex"],"prefix":"10.1186","volume":"38","author":[{"given":"Xiao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Jie","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianzi","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen He","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsong","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Xiang","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Qiang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,1,21]]},"reference":[{"key":"1025_CR1","doi-asserted-by":"publisher","unstructured":"Ci Y, Qiao J, Han M. Molecular mechanisms and metabolomics of natural polyphenols interfering with breast cancer metastasis. Molecules. 2016. https:\/\/doi.org\/10.3390\/molecules21121634 .","DOI":"10.3390\/molecules21121634"},{"key":"1025_CR2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21442","volume":"68","author":"RL Siegel","year":"2018","unstructured":"Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7\u201330.","journal-title":"CA Cancer J Clin"},{"key":"1025_CR3","doi-asserted-by":"publisher","first-page":"4951","DOI":"10.1158\/0008-5472.CAN-09-0099","volume":"69","author":"J Lu","year":"2009","unstructured":"Lu J, Steeg PS, Price JE, Krishnamurthy S, Mani SA, Reuben J, et al. Breast cancer metastasis: challenges and opportunities. Cancer Res. 2009;69:4951\u20133.","journal-title":"Cancer Res"},{"key":"1025_CR4","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/S0962-8924(03)00002-3","volume":"13","author":"H Gu","year":"2003","unstructured":"Gu H, Neel BG. The \u201cgab\u201d in signal transduction. Trends Cell Biol. 2003;13:122\u201330.","journal-title":"Trends Cell Biol"},{"key":"1025_CR5","doi-asserted-by":"publisher","first-page":"3695","DOI":"10.1128\/MCB.20.10.3695-3704.2000","volume":"20","author":"M Itoh","year":"2000","unstructured":"Itoh M, Yoshida Y, Nishida K, Narimatsu M, Hibi M, Hirano T. Role of Gab1 in heart, placenta, and skin development and growth factor- and cytokine-induced extracellular signal-regulated kinase mitogen-activated protein kinase activation. Mol Cell Biol. 2000;20:3695\u2013704.","journal-title":"Mol Cell Biol"},{"key":"1025_CR6","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/nm1341","volume":"12","author":"M Bentires-Alj","year":"2006","unstructured":"Bentires-Alj M, Gil SG, Chan R, Wang ZC, Wang Y, Imanaka N, et al. A role for the scaffolding adapter GAB2 in breast cancer. Nat Med. 2006;12:114\u201321.","journal-title":"Nat Med"},{"key":"1025_CR7","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.2353\/ajpath.2009.080543","volume":"174","author":"B Horst","year":"2009","unstructured":"Horst B, Gruvberger-Saal SK, Hopkins BD, Bordone L, Yang Y, Chernoff KA, et al. Gab2-mediated signaling promotes melanoma metastasis. Am J Pathol. 2009;174:1524\u201333.","journal-title":"Am J Pathol"},{"key":"1025_CR8","doi-asserted-by":"publisher","first-page":"4036","DOI":"10.1038\/onc.2015.472","volume":"35","author":"C Duckworth","year":"2016","unstructured":"Duckworth C, Zhang L, Carroll SL, Ethier SP, Cheung HW. Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression. Oncogene. 2016;35:4036\u201347.","journal-title":"Oncogene"},{"key":"1025_CR9","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1002\/ijc.27763","volume":"132","author":"A Hoeben","year":"2013","unstructured":"Hoeben A, Martin D, Clement PM, Cools J, Gutkind JS. Role of GRB2-associated binder 1 in epidermal growth factor receptor-induced signaling in head and neck squamous cell carcinoma. Int J Cancer. 2013;132:1042\u201350.","journal-title":"Int J Cancer"},{"key":"1025_CR10","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1093\/carcin\/bgn009","volume":"29","author":"I Seiden-Long","year":"2008","unstructured":"Seiden-Long I, Navab R, Shih W, Li M, Chow J, Zhu CQ, et al. Gab1 but not Grb2 mediates tumor progression in met overexpressing colorectal cancer cells. Carcinogenesis. 2008;29:647\u201355.","journal-title":"Carcinogenesis"},{"key":"1025_CR11","doi-asserted-by":"publisher","first-page":"6970","DOI":"10.1038\/onc.2008.347","volume":"27","author":"S Etienne-Manneville","year":"2008","unstructured":"Etienne-Manneville S. Polarity proteins in migration and invasion. Oncogene. 2008;27:6970\u201380.","journal-title":"Oncogene"},{"key":"1025_CR12","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1038\/ncb433","volume":"9","author":"A Wodarz","year":"2007","unstructured":"Wodarz A, Nathke I. Cell polarity in development and cancer. Nat Cell Biol. 2007;9:1016\u201324.","journal-title":"Nat Cell Biol"},{"key":"1025_CR13","doi-asserted-by":"publisher","first-page":"694","DOI":"10.7150\/jca.11709","volume":"6","author":"XM Li","year":"2015","unstructured":"Li XM, Wang H, Zhu LL, Zhao RZ, Ji HL. Genes regulating epithelial polarity are critical suppressors of esophageal oncogenesis. J Cancer. 2015;6:694\u2013700.","journal-title":"J Cancer"},{"key":"1025_CR14","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1038\/onc.2015.184","volume":"35","author":"K Zhang","year":"2016","unstructured":"Zhang K, Zhao H, Ji Z, Zhang C, Zhou P, Wang L, et al. Shp2 promotes metastasis of prostate cancer by attenuating the PAR3\/PAR6\/aPKC polarity protein complex and enhancing epithelial-to-mesenchymal transition. Oncogene. 2016;35:1271\u201382.","journal-title":"Oncogene"},{"key":"1025_CR15","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.molcel.2012.06.037","volume":"47","author":"Z Yang","year":"2012","unstructured":"Yang Z, Xue B, Umitsu M, Ikura M, Muthuswamy SK, Neel BG. The signaling adaptor Gab1 regulates cell polarity by acting as a PAR protein scaffold. Mol Cell. 2012;47:469\u201383.","journal-title":"Mol Cell"},{"key":"1025_CR16","unstructured":"Oncomine database. US Michigan, Ann Arbor. 2006. For Ma Breast 4 et al. https:\/\/www.oncomine.org\/resource\/main.html#d%3A18257966%3Bdso%3AgeneOverex%3Bdt%3Adataset%3Bec%3A%5B2%2C1%5D%3Bepv%3A150001.151078%2C2937%2C3508%3Bet%3Aover%3Bf%3A1889146%3Bg%3A2549%3Bgt%3Abarchart%3Bp%3A200001333%3Bpg%3A1%3Bpvf%3A2967%2C13105%2C150004%3Bscr%3Adatasets%3Bss%3Aall%3Bv%3A18 . Acessed 20 July 2017."},{"key":"1025_CR17","unstructured":"Oncomine database. US Michigan, Ann Arbor. 2006. For Richardson et al. https:\/\/www.oncomine.org\/resource\/main.html#d%3A156636655%3Bdso%3AgeneOverex%3Bdt%3Adataset%3Bec%3A%5B2%2C1%5D%3Bepv%3A150001.151078%2C2937%2C3508%3Bet%3Aover%3Bf%3A133687377%3Bg%3A2549%3Bgt%3Abarchart%3Bp%3A200010737%3Bpg%3A1%3Bpvf%3A2967%2C13105%2C150004%3Bscr%3Adatasets%3Bss%3Aall%3Bv%3A18 . Acessed 20 July 2017."},{"key":"1025_CR18","unstructured":"Oncomine database. US Michigan, Ann Arbor. 2006. For Nikolsky et al. https:\/\/www.oncomine.org\/resource\/main.html#d%3A1793%3Bdso%3AgeneOverex%3Bdt%3Adataset%3Bec%3A%5B2%2C1%5D%3Bepv%3A150001.151078%2C2937%2C3508%3Bet%3Aover%3Bf%3A3033603%3Bg%3A2549%3Bgt%3Abarchart%3Bp%3A94244277%3Bpg%3A1%3Bpvf%3A2967%2C13105%3Bscr%3Adatasets%3Bss%3Aall%3Bv%3A18 . Acessed 20 July 2017."},{"key":"1025_CR19","unstructured":"Oncomine database. US Michigan, Ann Arbor. 2006. For Ma Breast 3 et al. https:\/\/www.oncomine.org\/resource\/main.html#d%3A148784477%3Bdso%3AgeneOverex%3Bdt%3Adataset%3Bec%3A%5B2%2C1%5D%3Bepv%3A150001.151078%2C2937%2C3508%3Bet%3Aover%3Bf%3A146619767%3Bg%3A2549%3Bgt%3Abarchart%3Bp%3A148831897%3Bpg%3A1%3Bpvf%3A2967%2C13105%3Bscr%3Adatasets%3Bss%3Aall%3Bv%3A18 . Acessed 20 July 2017."},{"key":"1025_CR20","doi-asserted-by":"publisher","first-page":"6303","DOI":"10.1038\/sj.onc.1208776","volume":"24","author":"V Falco De","year":"2005","unstructured":"De Falco V, Guarino V, Malorni L, Cirafici AM, Troglio F, Erreni M, et al. RAI(ShcC\/N-Shc)-dependent recruitment of GAB 1 to RET oncoproteins potentiates PI 3-K signalling in thyroid tumors. Oncogene. 2005;24:6303\u201313.","journal-title":"Oncogene"},{"key":"1025_CR21","doi-asserted-by":"crossref","first-page":"11595","DOI":"10.18632\/oncotarget.7292","volume":"7","author":"W Sun","year":"2016","unstructured":"Sun W, Zhang Z, Wang J, Shang R, Zhou L, Wang X, et al. MicroRNA-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the GAB1-ERK axis. Oncotarget. 2016;7:11595\u2013608.","journal-title":"Oncotarget"},{"key":"1025_CR22","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1128\/MCB.20.4.1448-1459.2000","volume":"20","author":"GA Rodrigues","year":"2000","unstructured":"Rodrigues GA, Falasca M, Zhang Z, Ong SH, Schlessinger J. A novel positive feedback loop mediated by the docking protein Gab1 and phosphatidylinositol 3-kinase in epidermal growth factor receptor signaling. Mol Cell Biol. 2000;20:1448\u201359.","journal-title":"Mol Cell Biol"},{"key":"1025_CR23","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.semcancer.2012.03.007","volume":"22","author":"G Lorusso","year":"2012","unstructured":"Lorusso G, R\u00fcegg C. New insights into the mechanisms of organ-specific breast cancer metastasis. Semin Cancer Biol. 2012;22:226\u201333.","journal-title":"Semin Cancer Biol"},{"key":"1025_CR24","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1007\/s10555-007-9085-8","volume":"26","author":"SA Rabbani","year":"2007","unstructured":"Rabbani SA, Mazar AP. Evaluating distant metastases in breast cancer: from biology to outcomes. Cancer Metastasis Rev. 2007;26:663\u201374.","journal-title":"Cancer Metastasis Rev"},{"key":"1025_CR25","doi-asserted-by":"publisher","unstructured":"Mendez O, Peg V, Salvans C, Pujals M, Fernandez Y, Abasolo I, et al. Extracellular HMGA1 promotes tumor invasion and metastasis in triple-negative breast Cancer. Clin Cancer Res. 2018. https:\/\/doi.org\/10.1158\/1078-0432.CCR-18-0517 .","DOI":"10.1158\/1078-0432.CCR-18-0517"},{"key":"1025_CR26","doi-asserted-by":"publisher","unstructured":"Ye L, Li F, Song Y, Yu D, Xiong Z, Li Y, et al. Overexpression of CDCA7 predicts poor prognosis and induces EZH2-mediated progression of triple-negative breast Cancer. Int J Cancer. 2018. https:\/\/doi.org\/10.1002\/ijc.31766 .","DOI":"10.1002\/ijc.31766"},{"key":"1025_CR27","doi-asserted-by":"publisher","first-page":"2310","DOI":"10.1002\/ijc.29607","volume":"137","author":"R Bai","year":"2015","unstructured":"Bai R, Weng C, Dong H, Li S, Chen G, Xu Z. MicroRNA-409-3p suppresses colorectal cancer invasion and metastasis partly by targeting GAB1 expression. Int J Cancer. 2015;137:2310\u201322.","journal-title":"Int J Cancer"},{"key":"1025_CR28","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1620\/tjem.239.177","volume":"239","author":"L Hu","year":"2016","unstructured":"Hu L, Liu R. Expression of Gab1 is associated with poor prognosis of patients with epithelial ovarian Cancer. Tohoku J Exp Med. 2016;239:177\u201384.","journal-title":"Tohoku J Exp Med"},{"key":"1025_CR29","doi-asserted-by":"publisher","first-page":"e81347","DOI":"10.1371\/journal.pone.0081347","volume":"8","author":"H Sang","year":"2013","unstructured":"Sang H, Li T, Li H, Liu J. Down-regulation of Gab1 inhibits cell proliferation and migration in hilar cholangiocarcinoma. PLoS One. 2013;8:e81347.","journal-title":"PLoS One"},{"key":"1025_CR30","doi-asserted-by":"publisher","first-page":"e1004021","DOI":"10.1371\/journal.pcbi.1004021","volume":"11","author":"L Chen","year":"2015","unstructured":"Chen L, Du-Cuny L, Moses S, Dumas S, Song Z, Rezaeian AH, et al. Novel inhibitors induce large conformational changes of GAB1 Pleckstrin homology domain and kill breast Cancer cells. PLoS Comput Biol. 2015;11:e1004021.","journal-title":"PLoS Comput Biol"},{"key":"1025_CR31","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.ccr.2012.10.003","volume":"22","author":"LM McCaffrey","year":"2012","unstructured":"McCaffrey LM, Montalbano J, Mihai C, Macara IG. Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis. Cancer Cell. 2012;22:601\u201314.","journal-title":"Cancer Cell"},{"key":"1025_CR32","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1101\/gad.284166.116","volume":"30","author":"G Fan","year":"2016","unstructured":"Fan G, Zhang S, Gao Y, Greer PA, Tonks NK. HGF-independent regulation of MET and GAB1 by nonreceptor tyrosine kinase FER potentiates metastasis in ovarian cancer. Genes Dev. 2016;30:1542\u201357.","journal-title":"Genes Dev"}],"container-title":["Journal of Experimental & Clinical Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-019-1025-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13046-019-1025-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-019-1025-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T02:09:39Z","timestamp":1606097379000},"score":1,"resource":{"primary":{"URL":"https:\/\/jeccr.biomedcentral.com\/articles\/10.1186\/s13046-019-1025-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,21]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["1025"],"URL":"https:\/\/doi.org\/10.1186\/s13046-019-1025-2","relation":{},"ISSN":["1756-9966"],"issn-type":[{"value":"1756-9966","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,21]]},"assertion":[{"value":"12 September 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Investigation has been conducted in accordance with the ethical standards and according to the Declaration of Helsinki and national and international guidelines. Human tissues used in this study were reviewed and approved by the Committee for Ethical Review of Research Involving Human Subjects at Ren Ji Hospital. Informed consent was obtained from each patient. All animal studies were performed according to the protocols approved by the Renji Hospital Medical Experimental Animal Care Commission.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"27"}}