{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T06:04:51Z","timestamp":1776492291963,"version":"3.51.2"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Exp Clin Cancer Res"],"published-print":{"date-parts":[[2016,12]]},"DOI":"10.1186\/s13046-016-0385-0","type":"journal-article","created":{"date-parts":[[2016,7,20]],"date-time":"2016-07-20T15:55:39Z","timestamp":1469030139000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["SYNJ2BP inhibits tumor growth and metastasis by activating DLL4 pathway in hepatocellular carcinoma"],"prefix":"10.1186","volume":"35","author":[{"given":"Xiao","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangjiao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianwei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiongying","family":"Miao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,7,20]]},"reference":[{"issue":"2","key":"385_CR1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3322\/caac.21262","volume":"65","author":"LA Torre","year":"2015","unstructured":"Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87\u2013108.","journal-title":"CA Cancer J Clin"},{"issue":"14","key":"385_CR2","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1200\/JCO.2009.27.4456","volume":"28","author":"YE Al","year":"2010","unstructured":"Al YE. Nomograms for risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J Clin Oncol. 2010;28(14):2437\u201344.","journal-title":"J Clin Oncol"},{"issue":"9822","key":"385_CR3","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/S0140-6736(11)61347-0","volume":"379","author":"A Forner","year":"2012","unstructured":"Forner A, Llovet JM, Bruix J. Hepatocellular carcinomalancet. Lancet. 2012;379(9822):1245\u201355.","journal-title":"Lancet"},{"issue":"6","key":"385_CR4","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1002\/hep.22580","volume":"48","author":"RN Aravalli","year":"2008","unstructured":"Aravalli RN, Steer CJ, Cressman EN. Molecular mechanisms of hepatocellular carcinoma. Hepatology. 2008;48(6):2047\u201363.","journal-title":"Hepatology"},{"issue":"5","key":"385_CR5","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/ng.804","volume":"43","author":"Y Totoki","year":"2011","unstructured":"Totoki Y, Tatsuno K, Yamamoto S, Arai Y, Hosoda F, Ishikawa S, Tsutsumi S, Sonoda K, Totsuka H, Shirakihara T, et al. High-resolution characterization of a hepatocellular carcinoma genome. Nat Genet. 2011;43(5):464\u20139.","journal-title":"Nat Genet"},{"issue":"6","key":"385_CR6","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1002\/hep.25933","volume":"56","author":"CM Tsao","year":"2012","unstructured":"Tsao CM, Yan MD, Shih YL, Yu PN, Kuo CC, Lin WC, Li HJ, Lin YW. SOX1 functions as a tumor suppressor by antagonizing the WNT\/beta-catenin signaling pathway in hepatocellular carcinoma. Hepatology. 2012;56(6):2277\u201387.","journal-title":"Hepatology"},{"issue":"1","key":"385_CR7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13046-015-0121-1","volume":"34","author":"X Xu","year":"2015","unstructured":"Xu X, Liu Z, Zhou L, Xie H, Cheng J, Ling Q, Wang J, Guo H, Wei X, Zheng S. Characterization of genome-wide TFCP2 targets in hepatocellular carcinoma: implication of targets FN1 and TJP1 in metastasis. J Exp Clin Canc Res. 2015;34(1):6.","journal-title":"J Exp Clin Canc Res"},{"key":"385_CR8","doi-asserted-by":"publisher","unstructured":"He F, Li J, Xu J, Zhang S, Xu Y, Zhao W, Yin Z, Wang X. Decreased expression of ARID1A associates with poor prognosis and promotes metastases of hepatocellular carcinoma. J Exp Clin Canc Res. 2015;34(47). doi: 10.1186\/s13046-015-0164-3 .","DOI":"10.1186\/s13046-015-0164-3"},{"issue":"3","key":"385_CR9","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ccr.2012.07.023","volume":"22","author":"P Yang","year":"2012","unstructured":"Yang P, Li Q, Feng Y, Zhang Y, Markowitz GJ, Ning S, Deng Y, Zhao J, Jiang S, Yuan Y, et al. TGF-\u03b2-miR-34a-CCL22 signaling-induced treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma. Cancer Cell. 2012;22(3):291\u2013303.","journal-title":"Cancer Cell"},{"issue":"1","key":"385_CR10","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13046-015-0136-7","volume":"34","author":"L Deng","year":"2015","unstructured":"Deng L, Yang S, Xu F, Zhang J. Long noncoding RNA CCAT1 promotes hepatocellular carcinoma progression by functioning as let-7 sponge. J Exp Clin Canc Res. 2015;34(1):18.","journal-title":"J Exp Clin Canc Res"},{"key":"385_CR11","doi-asserted-by":"publisher","unstructured":"Wu J, Zhang J, Shen B, Yin K, Xu J, Gao W, Zhang L. Long noncoding RNA lncTCF7, induced by IL-6\/STAT3 transactivation, promotes hepatocellular carcinoma aggressiveness through epithelial-mesenchymal transition. J Exp Clin Canc Res. 2015;34(116). doi: 10.1186\/s13046-015-0229-3 .","DOI":"10.1186\/s13046-015-0229-3"},{"issue":"6","key":"385_CR12","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.ccr.2014.05.016","volume":"25","author":"CH Ries","year":"2014","unstructured":"Ries CH, Cannarile MA, Hoves S, Benz J, Wartha K, Runza V, Rey-Giraud F, Pradel LP, Feuerhake F, Klaman I, et al. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell. 2014;25(6):846\u201359.","journal-title":"Cancer Cell"},{"issue":"11","key":"385_CR13","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1093\/emboj\/18.11.2991","volume":"18","author":"Y Nemoto","year":"1999","unstructured":"Nemoto Y, De Camilli P. Recruitment of an alternatively spliced form of synaptojanin 2 to mitochondria by the interaction with the PDZ domain of a mitochondrial outer membrane protein. Embo J. 1999;18(11):2991\u20133006.","journal-title":"Embo J"},{"issue":"21","key":"385_CR14","doi-asserted-by":"crossref","first-page":"19008","DOI":"10.1074\/jbc.M112472200","volume":"277","author":"T Matsuzaki","year":"2002","unstructured":"Matsuzaki T. Regulation of endocytosis of activin type II receptors by a novel PDZ protein through Ral\/Ral-binding protein 1-dependent pathway. J Biol Chem. 2002;277(21):19008\u201318.","journal-title":"J Biol Chem"},{"issue":"5","key":"385_CR15","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1177\/153537020623100507","volume":"231","author":"YG Chen","year":"2006","unstructured":"Chen YG, Wang Q, Lin SL, Chang CD, Chuang J, Ying SY. Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis. Exp Biol Med (Maywood). 2006;231(5):534\u201344.","journal-title":"Exp Biol Med (Maywood)"},{"issue":"11","key":"385_CR16","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1161\/CIRCRESAHA.113.301686","volume":"113","author":"MG Adam","year":"2013","unstructured":"Adam MG, Berger C, Feldner A, Yang WJ, Wustehube-Lausch J, Herberich SE, Pinder M, Gesierich S, Hammes HP, Augustin HG, et al. Synaptojanin-2 binding protein stabilizes the Notch ligands DLL1 and DLL4 and inhibits sprouting angiogenesis. Circ Res. 2013;113(11):1206\u201318.","journal-title":"Circ Res"},{"issue":"7129","key":"385_CR17","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/nature05571","volume":"445","author":"M Hellstr\u00f6m","year":"2007","unstructured":"Hellstr\u00f6m M, Phng L, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, Alva J, Nilsson A, Karlsson L, Gaiano N, et al. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature. 2007;445(7129):776\u201380.","journal-title":"Nature"},{"issue":"28","key":"385_CR18","doi-asserted-by":"crossref","first-page":"12640","DOI":"10.1073\/pnas.1000132107","volume":"107","author":"J W\u00fcstehube","year":"2010","unstructured":"W\u00fcstehube J, Bartol A, Liebler SS, Br\u00fctsch R, Zhu Y, Felbor U, Sure U, Augustin HG, Fischer A. Cerebral cavernous malformation protein CCM1 inhibits sprouting angiogenesis by activating DELTA-NOTCH signaling. Proc Natl Acad Sci U S A. 2010;107(28):12640\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"385_CR19","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646\u201374.","journal-title":"Cell"},{"issue":"11","key":"385_CR20","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/nm.2537","volume":"17","author":"SM Weis","year":"2011","unstructured":"Weis SM, Cheresh DA. Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med. 2011;17(11):1359\u201370.","journal-title":"Nat Med"},{"issue":"6","key":"385_CR21","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1053\/j.gastro.2012.10.025","volume":"143","author":"M Strazzabosco","year":"2012","unstructured":"Strazzabosco M, Fabris L. Notch signaling in hepatocellular carcinoma: guilty in association! Gastroenterology. 2012;143(6):1430\u20134.","journal-title":"Gastroenterology"},{"key":"385_CR22","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/978-1-4614-0899-4_13","volume":"727","author":"J Wang","year":"2012","unstructured":"Wang J, Sullenger BA, Rich JN. NOTCH signaling in embryology and cancer. Adv Exp Med Biol. 2012;727:174\u201385.","journal-title":"Adv Exp Med Biol"},{"issue":"1","key":"385_CR23","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.gde.2006.12.001","volume":"17","author":"M Roy","year":"2007","unstructured":"Roy M, Pear WS, Aster JC. The multifaceted role of Notch in cancer. Curr Opin Genet Dev. 2007;17(1):52\u20139.","journal-title":"Curr Opin Genet Dev"},{"issue":"5","key":"385_CR24","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nrc3035","volume":"11","author":"P Ranganathan","year":"2011","unstructured":"Ranganathan P, Weaver KL, Capobianco AJ. Notch signalling in solid tumours: a little bit of everything but not all the time. Nat Rev Cancer. 2011;11(5):338\u201351.","journal-title":"Nat Rev Cancer"},{"key":"385_CR25","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S0046-8177(96)90006-4","volume":"21","author":"M Shimizu","year":"1990","unstructured":"Shimizu M, Saitoh Y, Itoh H. Immunohistochemical staining of Ha-rus oncogene product in normal, benign, and malignant human pancreatic tissues. Hum Pathol. 1990;21:607\u201312.","journal-title":"Hum Pathol"},{"issue":"8","key":"385_CR26","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1158\/0008-5472.CAN-07-2696","volume":"68","author":"SW Chan","year":"2008","unstructured":"Chan SW, Lim CJ, Guo K, Ng CP, Lee I, Hunziker W, Zeng Q, Hong W. A role for TAZ in migration, invasion, and tumorigenesis of breast cancer cells. Cancer Res. 2008;68(8):2592\u20138.","journal-title":"Cancer Res"},{"issue":"7162","key":"385_CR27","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nature06188","volume":"449","author":"AE Karnoub","year":"2007","unstructured":"Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449(7162):557\u201363.","journal-title":"Nature"},{"issue":"15","key":"385_CR28","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1038\/sj.onc.1205300","volume":"21","author":"G Fiucci","year":"2002","unstructured":"Fiucci G, Ravid D, Reich R, Liscovitch M. Caveolin-1 inhibits anchorage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells. Oncogene. 2002;21(15):2365\u201375.","journal-title":"Oncogene"},{"issue":"3","key":"385_CR29","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S1535-6108(04)00051-0","volume":"5","author":"C Garcia-Echeverria","year":"2004","unstructured":"Garcia-Echeverria C, Pearson MA, Marti A, Meyer T, Mestan J, Zimmermann J, Gao J, Brueggen J, Capraro HG, Cozens R, et al. In vivo antitumor activity of NVP-AEW541-A novel, potent, and selective inhibitor of the IGF-IR kinase. Cancer Cell. 2004;5(3):231\u20139.","journal-title":"Cancer Cell"},{"issue":"6","key":"385_CR30","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1002\/hep.24595","volume":"54","author":"JF Zhang","year":"2011","unstructured":"Zhang JF, He ML, Fu WM, Wang H, Chen LZ, Zhu X, Chen Y, Xie D, Lai P, Chen G, et al. Primate-specific microRNA-637 inhibits tumorigenesis in hepatocellular carcinoma by disrupting signal transducer and activator of transcription 3 signaling. Hepatology. 2011;54(6):2137\u201348.","journal-title":"Hepatology"},{"key":"385_CR31","doi-asserted-by":"crossref","unstructured":"Li Y, Tian B, Yang J, Zhao L, Wu X, Ye S, Liu Y, Tang Z. Stepwise metastatic human hepatocellular carcinoma cell model system with multiple metastatic potentials established through consecutive in vivo selection and studies on metastatic characteristics. J Cancer Res Clin. 2004;130(8):460-8.","DOI":"10.1007\/s00432-004-0564-9"},{"issue":"2-3","key":"385_CR32","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s10911-007-9046-4","volume":"12","author":"D Kedrin","year":"2007","unstructured":"Kedrin D, van Rheenen J, Hernandez L, Condeelis J, Segall JE. Cell motility and cytoskeletal regulation in invasion and metastasis. J Mammary Gland Biol. 2007;12(2-3):143\u201352.","journal-title":"J Mammary Gland Biol"},{"key":"385_CR33","first-page":"3094","volume":"14","author":"JL Li","year":"2009","unstructured":"Li JL, Harris AL. Crosstalk of VEGF and Notch pathways in tumour angiogenesis: therapeutic implications. Front Biosci (Landmark Ed). 2009;14:3094\u2013110.","journal-title":"Front Biosci (Landmark Ed)"},{"issue":"3","key":"385_CR34","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1097\/SLA.0b013e31820d944f","volume":"253","author":"NN Rahbari","year":"2011","unstructured":"Rahbari NN, Mehrabi A, Mollberg NM, M\u00fcller SA, Koch M, B\u00fcchler MW, Weitz J. Hepatocellular carcinoma. Ann Surg. 2011;253(3):453\u201369.","journal-title":"Ann Surg"},{"issue":"12","key":"385_CR35","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1056\/NEJMra1001683","volume":"365","author":"HB El-Serag","year":"2011","unstructured":"El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118\u201327.","journal-title":"N Engl J Med"},{"issue":"2","key":"385_CR36","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.ygcen.2009.01.020","volume":"161","author":"H Liu","year":"2009","unstructured":"Liu H, Chen F, Ge J, Wang Y, Zhang C, Cui X, Yu F, Tai G, Liu Z. Expression and localization of activin receptor-interacting protein 2 in mouse tissues. Gen Comp Endocr. 2009;161(2):276\u201382.","journal-title":"Gen Comp Endocr"},{"issue":"7","key":"385_CR37","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1111\/j.1478-3231.2007.01544.x","volume":"27","author":"L Gramantieri","year":"2007","unstructured":"Gramantieri L, Giovannini C, Lanzi A, Chieco P, Ravaioli M, Venturi A, Grazi GL, Bolondi L. Aberrant Notch3 and Notch4 expression in human hepatocellular carcinoma. Liver Int. 2007;27(7):997\u20131007.","journal-title":"Liver Int"},{"issue":"3","key":"385_CR38","first-page":"453","volume":"33","author":"K Yoshinaga","year":"2008","unstructured":"Yoshinaga K, Mimori K, Inoue H, Kamohara Y, Yamashita K. Activin A enhances MMP-7 activity via the transcription factor AP-1 in an esophageal squamous cell carcinoma cell line. Int J Oncol. 2008;33(3):453\u20139.","journal-title":"Int J Oncol"},{"issue":"11","key":"385_CR39","doi-asserted-by":"crossref","first-page":"5686","DOI":"10.1158\/0008-5472.CAN-05-3821","volume":"66","author":"J Krneta","year":"2006","unstructured":"Krneta J. Dissociation of angiogenesis and tumorigenesis in follistatin- and activin-expressing tumors. Cancer Res. 2006;66(11):5686\u201395.","journal-title":"Cancer Res"},{"issue":"1","key":"385_CR40","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3390\/cancers7010070","volume":"7","author":"H Loomans","year":"2015","unstructured":"Loomans H, Andl C. Intertwining of activin a and TGF\u03b2 signaling: dual roles in cancer progression and cancer cell invasion. Cancers. 2015;7(1):70\u201391.","journal-title":"Cancers"},{"issue":"9","key":"385_CR41","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.1073\/pnas.0611177104","volume":"104","author":"S Suchting","year":"2007","unstructured":"Suchting S, Freitas C, le Noble F, Benedito R, Breant C, Duarte A, Eichmann A. The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching. Proc Natl Acad Sci U S A. 2007;104(9):3225\u201330.","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["Journal of Experimental & Clinical Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-016-0385-0","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,11]],"date-time":"2019-09-11T13:47:11Z","timestamp":1568209631000},"score":1,"resource":{"primary":{"URL":"http:\/\/jeccr.biomedcentral.com\/articles\/10.1186\/s13046-016-0385-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,20]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["385"],"URL":"https:\/\/doi.org\/10.1186\/s13046-016-0385-0","relation":{},"ISSN":["1756-9966"],"issn-type":[{"value":"1756-9966","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,20]]},"article-number":"115"}}