{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:38:42Z","timestamp":1790746722244,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T00:00:00Z","timestamp":1597363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA193815"],"award-info":[{"award-number":["CA193815"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Fascin is an actin-bundling protein that is critical for filopodial formation and other cellular cytoskeletal structures. An elevated expression of fascin has been observed in tumor cells and is correlated with a shorter survival of cancer patients. Given its roles in tumor cell migration and invasion, we have developed small-molecule fascin inhibitors to prevent and delay tumor metastasis. Here we report the characterization of a new fascin inhibitor in mice. In addition to its inhibitory effects on tumor metastasis, we also report that fascin inhibitors can decrease the growth of specific subtypes of cancers, including epidermal growth factor receptor (EGFR)-high triple-negative breast cancer, and activated B-cell subtypes of diffuse large B-cell lymphoma. Hence, fascin inhibitors can be used to not only inhibit tumor metastasis, but also decrease the tumor growth of specific cancer types.<\/jats:p>","DOI":"10.3390\/cancers12082287","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T13:00:18Z","timestamp":1597410018000},"page":"2287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Anti-Metastasis Fascin Inhibitors Decrease the Growth of Specific Subtypes of Cancers"],"prefix":"10.3390","volume":"12","author":[{"given":"Yufeng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Jillian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Novita Pharmaceuticals, Inc., New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA"},{"name":"Sandra and Edward Meyer Cancer Center, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/0092-8674(79)90154-5","article-title":"Formation of filopodia in coelomocytes: Localization of fascin, a 58,000 dalton actin cross-linking protein","volume":"17","author":"Otto","year":"1979","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/0022-2836(78)90345-5","article-title":"Separation and interaction of the major components of sea urchin actin gel","volume":"125","author":"Bryan","year":"1978","journal-title":"J. Mol. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1016\/S0021-9258(18)89183-9","article-title":"Purification and characterization of an F-actin-bundling 55-kilodalton protein from HeLa cells","volume":"260","author":"Matsumura","year":"1985","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1083\/jcb.200208059","article-title":"Formation of filopodia-like bundles in vitro from a dendritic network","volume":"160","author":"Vignjevic","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1083\/jcb.200603013","article-title":"Role of fascin in filopodial protrusion","volume":"174","author":"Vignjevic","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1158\/1078-0432.CCR-08-1789","article-title":"Fascin regulates prostate cancer cell invasion and is associated with metastasis and biochemical failure in prostate cancer","volume":"15","author":"Darnel","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0169-5002(03)00294-0","article-title":"Independent value of fascin immunoreactivity for predicting lymph node metastases in typical and atypical pulmonary carcinoids","volume":"42","author":"Pelosi","year":"2003","journal-title":"Lung Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1159\/000081327","article-title":"The prognostic relevance of fascin expression in human gastric carcinoma","volume":"67","author":"Hashimoto","year":"2004","journal-title":"Oncology"},{"key":"ref_9","first-page":"67","article-title":"Expression of mesothelin, fascin, and prostate stem cell antigen in primary ovarian mucinous tumors and their utility in differentiating primary ovarian mucinous tumors from metastatic pancreatic mucinous carcinomas in the ovary","volume":"24","author":"Cao","year":"2005","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1158\/1078-0432.CCR-05-2281","article-title":"Prognostic significance of basal-like phenotype and fascin expression in node-negative invasive breast carcinomas","volume":"12","author":"Sarrio","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"263","DOI":"10.4161\/cib.3.3.11556","article-title":"Fascin: Invasive filopodia promoting metastasis","volume":"3","author":"Machesky","year":"2010","journal-title":"Commun. Integr. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tan, V.Y., Lewis, S.J., Adams, J.C., and Martin, R.M. (2013). Association of fascin-1 with mortality, disease progression and metastasis in carcinomas: A systematic review and meta-analysis. BMC Med., 11.","DOI":"10.1186\/1741-7015-11-52"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1054\/bjoc.2000.1395","article-title":"Fascin, an actin-bundling protein associated with cell motility, is upregulated in hormone receptor negative breast cancer","volume":"83","author":"Grothey","year":"2000","journal-title":"Br. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1016\/j.biocel.2005.05.004","article-title":"Roles of fascin in human carcinoma motility and signaling: Prospects for a novel biomarker?","volume":"37","author":"Hashimoto","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1002\/cm.20356","article-title":"Fascin1 is dispensable for mouse development but is favorable for neonatal survival","volume":"66","author":"Yamakita","year":"2009","journal-title":"Cell Motil. Cytoskeleton"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1053\/j.gastro.2014.01.046","article-title":"Fascin is regulated by slug, promotes progression of pancreatic cancer in mice, and is associated with patient outcomes","volume":"146","author":"Li","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.ejcb.2014.08.002","article-title":"Conditional expression of fascin increases tumor progression in a mouse model of intestinal cancer","volume":"93","author":"Schoumacher","year":"2014","journal-title":"Eur. J. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7465","DOI":"10.1038\/ncomms8465","article-title":"Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization","volume":"6","author":"Huang","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.molonc.2016.03.006","article-title":"Improving fascin inhibitors to block tumor cell migration and metastasis","volume":"10","author":"Han","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.jmb.2018.03.009","article-title":"Structural Insights into the Induced-fit Inhibition of Fascin by a Small-Molecule Inhibitor","volume":"430","author":"Huang","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1023\/A:1018943613122","article-title":"Physiological parameters in laboratory animals and humans","volume":"10","author":"Davies","year":"1993","journal-title":"Pharm. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3772","DOI":"10.1073\/pnas.0500658102","article-title":"Synthetic analogues of migrastatin that inhibit mammary tumor metastasis in mice","volume":"102","author":"Shan","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ccr.2008.12.019","article-title":"Orai1 and STIM1 are critical for breast tumor cell migration and metastasis","volume":"15","author":"Yang","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1038\/nature08978","article-title":"Migrastatin analogues target fascin to block tumour metastasis","volume":"464","author":"Chen","year":"2010","journal-title":"Nature"},{"key":"ref_25","first-page":"1486","article-title":"Reduction of established spontaneous mammary carcinoma metastases following immunotherapy with major histocompatibility complex class II and B7.1 cell-based tumor vaccines","volume":"58","author":"Pulaski","year":"1998","journal-title":"Cancer Res."},{"key":"ref_26","first-page":"543","article-title":"Fascin, a sensitive new marker for Reed-Sternberg cells of hodgkin\u2019s disease. Evidence for a dendritic or B cell derivation?","volume":"150","author":"Pinkus","year":"1997","journal-title":"Am. J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1073\/pnas.1008969108","article-title":"Critical role of PI3K signaling for NF-kappaB-dependent survival in a subset of activated B-cell-like diffuse large B-cell lymphoma cells","volume":"108","author":"Kloo","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1158\/1078-0432.CCR-14-0384","article-title":"The novel IKK2 inhibitor LY2409881 potently synergizes with histone deacetylase inhibitors in preclinical models of lymphoma through the downregulation of NF-kappaB","volume":"21","author":"Deng","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.celrep.2015.03.050","article-title":"The proteomic landscape of triple-negative breast cancer","volume":"11","author":"Lawrence","year":"2015","journal-title":"Cell Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1242\/jcs.100.3.491","article-title":"Epidermal growth factor induces rapid reorganization of the actin microfilament system in human A431 cells","volume":"100","author":"Rijken","year":"1991","journal-title":"J. Cell Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/0014-4827(92)90465-K","article-title":"The epidermal growth factor receptor is associated with actin filaments","volume":"199","author":"Romeyn","year":"1992","journal-title":"Exp. Cell Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1083\/jcb.119.2.349","article-title":"The EGF receptor is an actin-binding protein","volume":"119","author":"Verkleij","year":"1992","journal-title":"J. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Weiss, L. (2000). Metastasis of cancer: A conceptual history from antiquity to the 1990s. Cancer Metastasis Rev., 19, I\u2013XI, 193\u2013383.","DOI":"10.1023\/A:1010623111204"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrc1098","article-title":"The pathogenesis of cancer metastasis: The \u2018seed and soil\u2019 hypothesis revisited","volume":"3","author":"Fidler","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.cell.2011.09.024","article-title":"Tumor metastasis: Molecular insights and evolving paradigms","volume":"147","author":"Valastyan","year":"2011","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1146\/annurev.cellbio.21.122303.120306","article-title":"The great escape: When cancer cells hijack the genes for chemotaxis and motility","volume":"21","author":"Condeelis","year":"2005","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1126\/science.1175862","article-title":"Actin, a central player in cell shape and movement","volume":"326","author":"Pollard","year":"2009","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nrm2406","article-title":"Filopodia: Molecular architecture and cellular functions","volume":"9","author":"Mattila","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_39","first-page":"507","article-title":"Phagocytosis of cross-linked gelatin matrix by human breast carcinoma cells correlates with their invasive capacity","volume":"4","author":"Coopman","year":"1998","journal-title":"Clin. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1529\/biophysj.104.056515","article-title":"The physics of filopodial protrusion","volume":"89","author":"Mogilner","year":"2005","journal-title":"Biophys. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.18632\/oncotarget.12284","article-title":"Triple-negative breast cancer: Is there a treatment on the horizon?","volume":"8","author":"Yao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s11912-017-0593-6","article-title":"Emerging Variants of Castration-Resistant Prostate Cancer","volume":"19","author":"Vlachostergios","year":"2017","journal-title":"Curr. Oncol. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nm.4341","article-title":"Biology and evolution of poorly differentiated neuroendocrine tumors","volume":"23","author":"Rickman","year":"2017","journal-title":"Nat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Al-Alwan, M., Olabi, S., Ghebeh, H., Barhoush, E., Tulbah, A., Al-Tweigeri, T., Ajarim, D., and Adra, C. (2011). Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027339"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1091\/mbc.E14-09-1384","article-title":"Prostaglandins regulate nuclear localization of Fascin and its function in nucleolar architecture","volume":"26","author":"Groen","year":"2015","journal-title":"Mol. Biol. Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.devcel.2016.07.021","article-title":"Fascin Regulates Nuclear Movement and Deformation in Migrating Cells","volume":"38","author":"Jayo","year":"2016","journal-title":"Dev. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"eaas9473","DOI":"10.1126\/scisignal.aas9473","article-title":"EGFR-induced cytoskeletal changes drive complex cell behaviors: The tip of the iceberg","volume":"11","author":"McClatchey","year":"2018","journal-title":"Sci. Signal."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"eaan0949","DOI":"10.1126\/scisignal.aan0949","article-title":"SILAC identifies LAD1 as a filamin-binding regulator of actin dynamics in response to EGF and a marker of aggressive breast tumors","volume":"11","author":"Roth","year":"2018","journal-title":"Sci. Signal."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"eaaq1060","DOI":"10.1126\/scisignal.aaq1060","article-title":"KIF22 coordinates CAR and EGFR dynamics to promote cancer cell proliferation","volume":"11","author":"Pike","year":"2018","journal-title":"Sci. Signal."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.tibs.2019.11.003","article-title":"The Cytoskeleton as Regulator of Cell Signaling Pathways","volume":"45","author":"Moujaber","year":"2020","journal-title":"Trends Biochem. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.cell.2015.12.042","article-title":"Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton","volume":"164","author":"Hu","year":"2016","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/j.1432-1033.1970.tb01016.x","article-title":"Binding of aldolase and triosephosphate dehydrogenase to F-actin and modification of catalytic properties of aldolase","volume":"15","author":"Arnold","year":"1970","journal-title":"Eur. J. Biochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6861","DOI":"10.1074\/jbc.271.12.6861","article-title":"The molecular nature of the F-actin binding activity of aldolase revealed with site-directed mutants","volume":"271","author":"Wang","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1172\/JCI71812","article-title":"DLC1-dependent parathyroid hormone-like hormone inhibition suppresses breast cancer bone metastasis","volume":"124","author":"Wang","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Nabbi, A., and Riabowol, K. (2015). Rapid Isolation of Nuclei from Cells In Vitro. Cold Spring Harb. Protoc., 769\u2013772.","DOI":"10.1101\/pdb.prot083733"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.3892\/ol.2015.3522","article-title":"Development of an orthotopic model of human metastatic prostate cancer in the NOD-SCIDgamma mouse (Mus musculus) anterior prostate","volume":"10","author":"Cifuentes","year":"2015","journal-title":"Oncol. Lett."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/8\/2287\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:01:06Z","timestamp":1760176866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/8\/2287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,14]]},"references-count":56,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["cancers12082287"],"URL":"https:\/\/doi.org\/10.3390\/cancers12082287","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,14]]}}}