{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:18:07Z","timestamp":1790144287929,"version":"4.0.1"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,9,30]],"date-time":"2014-09-30T00:00:00Z","timestamp":1412035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005984","name":"Dr. Miriam and Sheldon G. Adelson Medical Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005984","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ruth and Martin H. Weil Foundation"},{"name":"National Institute of Health"},{"DOI":"10.13039\/100000054","name":"National Cancer Institute, USA","doi-asserted-by":"crossref","award":["1R01CA167967-01A1"],"award-info":[{"award-number":["1R01CA167967-01A1"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute, USA","doi-asserted-by":"crossref","award":["P01CA029605"],"award-info":[{"award-number":["P01CA029605"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2015,1]]},"abstract":"Summary<\/jats:title>Melanoma brain metastasis (MBM<\/jats:styled-content>) is frequent and has a very poor prognosis with no current predictive factors or therapeutic molecular targets. Our study unravels the molecular alterations of cell\u2010surface glycoprotein CD<\/jats:styled-content>44 variants during melanoma progression to MBM<\/jats:styled-content>. High expression of CD<\/jats:styled-content>44 splicing variant 6 (CD<\/jats:styled-content>44v6) in primary melanoma (PRM<\/jats:styled-content>) and regional lymph node metastases from AJCC<\/jats:styled-content> Stage IIIC<\/jats:styled-content> patients significantly predicts MBM<\/jats:styled-content> development. The expression of CD<\/jats:styled-content>44v6 also enhances the migration of MBM<\/jats:styled-content> cells by hyaluronic acid and hepatocyte growth factor exposure. Additionally, CD<\/jats:styled-content>44v6\u2010positive MBM<\/jats:styled-content> migration is reduced by blocking with a CD<\/jats:styled-content>44v6\u2010specific monoclonal antibody or knocking down CD<\/jats:styled-content>44v6 by siRNA<\/jats:styled-content>. ESRP<\/jats:styled-content>1 and ESRP<\/jats:styled-content>2 splicing factors correlate with CD<\/jats:styled-content>44v6 expression in PRM<\/jats:styled-content>, and ESRP<\/jats:styled-content>1 knockdown significantly decreases CD<\/jats:styled-content>44v6 expression. However, an epigenetic silencing of ESRP<\/jats:styled-content>1 is observed in metastatic melanoma, specifically in MBM<\/jats:styled-content>. In advanced melanomas, CD<\/jats:styled-content>44v6 expression correlates with PTBP<\/jats:styled-content>1 and U2AF<\/jats:styled-content>2 splicing factors, and PTBP<\/jats:styled-content>1 knockdown significantly decreases CD<\/jats:styled-content>44v6 expression. Overall, these findings open a new avenue for understanding the high affinity of melanoma to progress to MBM<\/jats:styled-content>, suggesting CD<\/jats:styled-content>44v6 as a potential MBM<\/jats:styled-content>\u2010specific factor with theranostic utility for stratifying patients.<\/jats:p>","DOI":"10.1111\/pcmr.12307","type":"journal-article","created":{"date-parts":[[2014,8,28]],"date-time":"2014-08-28T15:31:44Z","timestamp":1409239904000},"page":"82-93","source":"Crossref","is-referenced-by-count":57,"title":["Brain metastasis is predetermined in early stages of cutaneous melanoma by CD44v6 expression through epigenetic regulation of the spliceosome"],"prefix":"10.1111","volume":"28","author":[{"given":"Diego M.","family":"Marzese","sequence":"first","affiliation":[{"name":"Department of Molecular Oncology John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie L.","family":"Huynh","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Hirose","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C.","family":"Donovan","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly T.","family":"Huynh","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Kiyohara","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald L.","family":"Morton","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garni","family":"Barkhoudarian","sequence":"additional","affiliation":[{"name":"Brain Tumor Center & Pituitary Disorders Program John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Brain Tumor Center & Pituitary Disorders Program John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave S. B.","family":"Hoon","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology John Wayne Cancer Institute Providence Saint John's Health Center Santa Monica CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204435"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00124-X"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.07.005"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90694-A"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.23.4799"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2012.08.011"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1097\/CMR.0b013e328361926c","article-title":"Melanoma\u2010related mortality and productivity losses in the USA, 1990\u20102008","volume":"23","author":"Bristow B.N.","year":"2013","journal-title":"Melanoma Res."},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44540"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.1.362-370.2006"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(20000215)85:4<523::AID-IJC13>3.0.CO;2-6"},{"key":"e_1_2_8_12_1","first-page":"3427","article-title":"Patterned distribution of metastases from malignant melanoma in humans","volume":"43","author":"Monte S.M.","year":"1983","journal-title":"Cancer Res."},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.06536-11"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10059-010-0133-9"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/mp.52.4.189"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2011.10.013"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.6.10.986"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e3182380f56"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1999.00804.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27324"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.03.019"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-0037"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gdata.2014.06.007"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt420"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nou107"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/ejso.2001.1133"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2011.08071.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-0801"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.6.3.14056"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1114066"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2010.02.024"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.242602"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053883"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.397125"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2007.10.009"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2004811"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1998.88.1.0011"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12307-009-0022-y"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.24.12160"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21208"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.09284"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.14.3821"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-3514"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-1361"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07385"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0910"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.02.009"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.4161\/rna.6.5.9606"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3294"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1892"}],"container-title":["Pigment Cell & Melanoma Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpcmr.12307","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpcmr.12307","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcmr.12307","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T08:03:06Z","timestamp":1695542586000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pcmr.12307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,30]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1111\/pcmr.12307"],"URL":"https:\/\/doi.org\/10.1111\/pcmr.12307","archive":["Portico"],"relation":{},"ISSN":["1755-1471","1755-148X"],"issn-type":[{"value":"1755-1471","type":"print"},{"value":"1755-148X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,30]]}}}