PMID- 25233929 OWN - NLM STAT- MEDLINE DCOM- 20150214 LR - 20180816 IS - 1460-2180 (Electronic) IS - 0143-3334 (Linking) VI - 35 IP - 12 DP - 2014 Dec TI - ETV5 transcription program links BDNF and promotion of EMT at invasive front of endometrial carcinomas. PG - 2679-86 LID - 10.1093/carcin/bgu198 [doi] AB - Myometrial infiltration represents a main clinical determinant of endometrial carcinomas (EC) presenting as aggressive high-grade deeply invasive neoplasms, substantially associated with risk of recurrence and death. The up-regulation of ETV5 transcription factor linked to the promotion of epithelial to mesenchymal transition is considered as a basic mechanism underlying the initial steps of EC invasion. In this work, we aimed to investigate the transcription program of tumor invasion regulated by ETV5. We performed a comparative Chip-on-chip analysis at invasive front and superficial area of human EC. ETV5 specific binding to promoter regions of genes related to cellular migration, adhesion and invasion at deep invasion tumor areas highlighted the relevance of neural networks associated with cellular plasticity. Interestingly, brain-derived neurotrophic factor (BDNF) demonstrated a principal role orchestrating ETV5-mediated epithelial-to-mesenchymal transition in endometrial cancer. Impairment of the BDNF/tropomyosin-related kinase B (TrkB)/extracellular signal-regulated kinase axis in endometrial cancer cell lines reversed the aggressive and invasive phenotype promoted by the up-regulation of ETV5 at the invasive front of EC. Likewise, BDNF directly impacted on the efficiency of ETV5 promoted metastasis in a mice model of endometrial distant dissemination. These results translate the recognized role of BDNF/TrkB on neural plasticity into a relevant cancer metastasis event; suggest common mechanisms shared by neural development and tumor invasion; and offer new therapeutic opportunities specifically directed against disseminated disease in endometrial cancer. CI - (c) The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. FAU - Alonso-Alconada, Lorena AU - Alonso-Alconada L AD - Translational Medical Oncology, Health Research Institute of Santiago (IDIS), Fundacion Ramon Dominguez, SERGAS, Trav. Choupana s/n, 15706 Santiago de Compostela, Spain, Oncology Pathology Group, Dept. de Ciencies Mediques Basiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomedica de Lleida, IRBLleida, 25198 Lleida, Spain, Liquid Biopsy Analysis Unit, Health Research Institute of Santiago (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Trav. Choupana s/n, 15706 Santiago de Compostela, Spain and Research Unit in Biomedicine, Vall d'Hebron Research Institute and Hospital and Universitat Autonoma de Barcelona, 08035 Barcelona, Spain. FAU - Eritja, Nuria AU - Eritja N AD - Oncology Pathology Group, Dept. de Ciencies Mediques Basiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomedica de Lleida, IRBLleida, 25198 Lleida, Spain. FAU - Muinelo-Romay, Laura AU - Muinelo-Romay L AD - Liquid Biopsy Analysis Unit, Health Research Institute of Santiago (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Trav. Choupana s/n, 15706 Santiago de Compostela, Spain and. FAU - Barbazan, Jorge AU - Barbazan J AD - Translational Medical Oncology, Health Research Institute of Santiago (IDIS), Fundacion Ramon Dominguez, SERGAS, Trav. Choupana s/n, 15706 Santiago de Compostela, Spain, Oncology Pathology Group, Dept. de Ciencies Mediques Basiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomedica de Lleida, IRBLleida, 25198 Lleida, Spain, Liquid Biopsy Analysis Unit, Health Research Institute of Santiago (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Trav. Choupana s/n, 15706 Santiago de Compostela, Spain and Research Unit in Biomedicine, Vall d'Hebron Research Institute and Hospital and Universitat Autonoma de Barcelona, 08035 Barcelona, Spain. FAU - Lopez-Lopez, Rafael AU - Lopez-Lopez R AD - Translational Medical Oncology, Health Research Institute of Santiago (IDIS), Fundacion Ramon Dominguez, SERGAS, Trav. Choupana s/n, 15706 Santiago de Compostela, Spain, Oncology Pathology Group, Dept. de Ciencies Mediques Basiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomedica de Lleida, IRBLleida, 25198 Lleida, Spain, Liquid Biopsy Analysis Unit, Health Research Institute of Santiago (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Trav. Choupana s/n, 15706 Santiago de Compostela, Spain and Research Unit in Biomedicine, Vall d'Hebron Research Institute and Hospital and Universitat Autonoma de Barcelona, 08035 Barcelona, Spain. FAU - Matias-Guiu, Xavier AU - Matias-Guiu X AD - Oncology Pathology Group, Dept. de Ciencies Mediques Basiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomedica de Lleida, IRBLleida, 25198 Lleida, Spain. FAU - Gil-Moreno, Antonio AU - Gil-Moreno A AD - Research Unit in Biomedicine, Vall d'Hebron Research Institute and Hospital and Universitat Autonoma de Barcelona, 08035 Barcelona, Spain. FAU - Dolcet, Xavier AU - Dolcet X AD - Oncology Pathology Group, Dept. de Ciencies Mediques Basiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomedica de Lleida, IRBLleida, 25198 Lleida, Spain. FAU - Abal, Miguel AU - Abal M AD - Translational Medical Oncology, Health Research Institute of Santiago (IDIS), Fundacion Ramon Dominguez, SERGAS, Trav. Choupana s/n, 15706 Santiago de Compostela, Spain, Oncology Pathology Group, Dept. de Ciencies Mediques Basiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomedica de Lleida, IRBLleida, 25198 Lleida, Spain, Liquid Biopsy Analysis Unit, Health Research Institute of Santiago (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Trav. Choupana s/n, 15706 Santiago de Compostela, Spain and Research Unit in Biomedicine, Vall d'Hebron Research Institute and Hospital and Universitat Autonoma de Barcelona, 08035 Barcelona, Spain miguel.abal.posada@sergas.es. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140918 PL - England TA - Carcinogenesis JT - Carcinogenesis JID - 8008055 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (DNA-Binding Proteins) RN - 0 (ETV5 protein, human) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factors) RN - 7171WSG8A2 (BDNF protein, human) SB - IM MH - Animals MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - *Cell Movement MH - Cell Proliferation MH - Chromatin Immunoprecipitation MH - DNA-Binding Proteins/*genetics/metabolism MH - Endometrial Neoplasms/genetics/*metabolism/*pathology MH - *Epithelial-Mesenchymal Transition MH - Female MH - Fluorescent Antibody Technique MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Mice MH - Neoplasm Invasiveness MH - RNA, Messenger/genetics MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Transcription Factors/*genetics/metabolism MH - Tumor Cells, Cultured EDAT- 2014/09/23 06:00 MHDA- 2015/02/15 06:00 CRDT- 2014/09/20 06:00 PHST- 2014/09/20 06:00 [entrez] PHST- 2014/09/23 06:00 [pubmed] PHST- 2015/02/15 06:00 [medline] AID - bgu198 [pii] AID - 10.1093/carcin/bgu198 [doi] PST - ppublish SO - Carcinogenesis. 2014 Dec;35(12):2679-86. doi: 10.1093/carcin/bgu198. Epub 2014 Sep 18.