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We show that the genetic context of cancer cells influence E2F1's role to impede the protumorigenic role. Thirty to fifty percent of melanoma patients carry mutant BRAF with about 90% of mutant BRAF melanomas being V<jats:sup>600E<\/jats:sup> mutation. Tissue microarrays from melanoma patients were used to establish an association between E2F1 and BRAF<jats:sup>V600E<\/jats:sup>. We show for the first time that low E2F1 levels in BRAF<jats:sup>V600E<\/jats:sup> melanomas are associated with lymph node metastasis. Genetic manipulation of E2F1 in BRAF<jats:sup>V600E<\/jats:sup> and BRAF<jats:sup>wt<\/jats:sup> cells were used to determine its role in malignant melanoma progression by examining effects on migration and invasion. E2F1\u2010mediated negative regulation of myosin light chain kinase (MYLK) increased migration and invasion in BRAF<jats:sup>V600E<\/jats:sup> cells by phosphorylating myosin light chain and increased stress fiber formation. We show that E2F1 inhibits extracellular signal\u2010regulated kinase (ERK) activation in BRAF<jats:sup>V600E<\/jats:sup> cells and provide evidence for a negative feedback loop between E2F1 and ERK in these cells. This study shows for the first time that E2F1 has a cancer protective role in oncogenic BRAF\u2010activated melanoma cells and that loss of E2F1 can allow disease progression through a novel mechanism of E2F1\u2010mediated MYLK regulation. This study has implications for oncogenic BRAF\u2010activated tumors and resistance to targeted oncogenic BRAF therapy.<\/jats:p>","DOI":"10.1002\/mc.23043","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T06:39:47Z","timestamp":1558679987000},"page":"1701-1710","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Contextual role of E2F1 in suppression of melanoma cell motility and invasiveness"],"prefix":"10.1002","volume":"58","author":[{"given":"Peng","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Cell Systems &amp; Anatomy, School of Medicine The University of Texas Health at San Antonio  San Antonio Texas"},{"name":"Department of Urology, School of Medicine The University of Texas Health at San Antonio  San Antonio Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roble G.","family":"Bedolla","sequence":"additional","affiliation":[{"name":"Department of Urology, School of Medicine The University of Texas Health at San Antonio  San Antonio Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiyoung","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine The University of Texas Health at San Antonio  San Antonio Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James E.","family":"Fitzpatrick","sequence":"additional","affiliation":[{"name":"Department of Dermatology, School of Medicine University of Colorado  Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Addanki P.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Urology, School of Medicine The University of Texas Health at San Antonio  San Antonio Texas"},{"name":"Department of Pharmacology, School of Medicine The University of Texas Health at San Antonio  San Antonio Texas"},{"name":"Department of Molecular Medicine, &amp; Mays Cancer Center, School of Medicine The University of Texas Health at San Antonio  San Antonio Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9282-4861","authenticated-orcid":false,"given":"Rita","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Urology, School of Medicine The University of Texas Health at San Antonio  San Antonio Texas"},{"name":"Department of Pharmacology, School of Medicine The University of Texas Health at San Antonio  San Antonio Texas"},{"name":"Department of Molecular Medicine, &amp; Mays Cancer Center, School of Medicine The University of Texas Health at San Antonio  San Antonio Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,5,23]]},"reference":[{"key":"e_1_2_6_1_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.326"},{"key":"e_1_2_6_1_3_1","first-page":"43","article-title":"MEK inhibitors and their potential in the treatment of advanced melanoma: the advantages of combination therapy","volume":"10","author":"Tran KA","year":"2016","journal-title":"Drug Des Devel Ther"},{"key":"e_1_2_6_1_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.6.1005"},{"key":"e_1_2_6_1_5_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.5.4.2512"},{"key":"e_1_2_6_1_6_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.5.6.2926"},{"key":"e_1_2_6_1_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-2196"},{"key":"e_1_2_6_1_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2309"},{"key":"e_1_2_6_1_9_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.10.8.15341"},{"key":"e_1_2_6_1_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027231"},{"key":"e_1_2_6_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.06.019"},{"key":"e_1_2_6_1_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1981.240.5.C222"},{"key":"e_1_2_6_1_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00260a019"},{"key":"e_1_2_6_1_14_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.05.00064704"},{"key":"e_1_2_6_1_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201100192"},{"key":"e_1_2_6_1_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq144"},{"key":"e_1_2_6_1_17_1","doi-asserted-by":"publisher","DOI":"10.1159\/000084511"},{"key":"e_1_2_6_1_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2010.56"},{"key":"e_1_2_6_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2005.12.017"},{"key":"e_1_2_6_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.05.028"},{"key":"e_1_2_6_1_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3131"},{"key":"e_1_2_6_1_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0562"},{"key":"e_1_2_6_1_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1664"},{"key":"e_1_2_6_1_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111956200"},{"key":"e_1_2_6_1_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-2647"},{"key":"e_1_2_6_1_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-276"},{"key":"e_1_2_6_1_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073436"},{"key":"e_1_2_6_1_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-0826"},{"key":"e_1_2_6_1_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp458"},{"key":"e_1_2_6_1_30_1","unstructured":"Lovly C Pao W Sosman J. 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