Abstract
Endometrial carcinoma (EC) is the most frequent among infiltrating tumors of the female genital tract, with myometrial invasion representing an increase in the rate of recurrences and a decrease in survival. We have previously described ETV5 transcription factor associated with myometrial infiltration in human ECs. In this work, we further investigated ETV5 orchestrating downstream effects to confer the tumor the invasive capabilities needed to disseminate in the early stages of EC dissemination. Molecular profiling evidenced ETV5 having a direct role on epithelial-to-mesenchymal transition (EMT). In particular, ETV5 modulated Zeb1 expression and E-Cadherin repression leading to a complete reorganization of cell–cell and cell–substrate contacts. ETV5-promoted EMT resulted in the acquisition of migratory and invasive capabilities in endometrial cell lines. Furthermore, we identified the lipoma-preferred partner protein as a regulatory partner of ETV5, acting as a sensor for extracellular signals promoting tumor invasion. All together, we propose ETV5-transcriptional regulation of the EMT process through a crosstalk with the tumor surrounding microenvironment, as a principal event initiating EC invasion.
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Acknowledgements
This work was supported by the Spanish Ministry of Science and Innovation (SAF 2005-06771; SAF 2008-03996), Spanish Ministry of Health (RTICC RD06/0020/0058; CP08/00142, PI08/0797), European Commission Program Fondo Europeo de Desarrollo Regional (FEDER), Catalan Institute of Health (DURSI 2005SGR00553), Fundacio La Marato de TV3 (grant 050431), ACCIO (RDITSCON07-1-0001), AECC (Grupos Estables de Investigacion 2011) and National Programme of Biotecnology (FIT-010000-2007-26). LAA and JB are recipients of fellowships from the Basque Government (Spain) and the Spanish Ministry of Education and Science, respectively.
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Colas, E., Muinelo-Romay, L., Alonso-Alconada, L. et al. ETV5 cooperates with LPP as a sensor of extracellular signals and promotes EMT in endometrial carcinomas. Oncogene 31, 4778–4788 (2012). https://doi.org/10.1038/onc.2011.632
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DOI: https://doi.org/10.1038/onc.2011.632
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