Sampedro Núñez, MiguelBouthelier, AntonioSerrano Somavilla, AnaMartínez Hernández, RebecaAdrados, MagdalenaMartín Pérez, ElenaMuñoz de Nova, José LuisCameselle Teijeiro, José ManuelBlanco Carrera, ConcepciónCabezas Agrícola, José ManuelDíaz, José ÁngelGarcía Centeno, RogelioAragonés, JuliánMarazuela, Mónica2020-11-302020-11-302020Sampedro-Núñez, M.; Bouthelier, A.; Serrano-Somavilla, A.; Martínez-Hernández, R.; Adrados, M.; Martín-Pérez, E.; Muñoz de Nova, J.L.; Cameselle-Teijeiro, J.M.; Blanco-Carrera, C.; Cabezas-Agricola, J.M.; Díaz, J.Á.; García-Centeno, R.; Aragones, J.; Marazuela, M. LAT-1 and GLUT-1 Carrier Expression and Its Prognostic Value in Gastroenteropancreatic Neuroendocrine Tumors. Cancers 2020, 12, 2968http://hdl.handle.net/10347/23865Cancer cells develop mechanisms that increase nutrient uptake, including key nutrient carriers, such as amino acid transporter 1 (LAT-1) and glucose transporter 1 (GLUT-1), regulated by the oxygen-sensing Von Hippel Lindau-hypoxia-inducible factor (VHL-HIF) transcriptional pathway. We aimed to analyze these metabolic players in gastroenteropancreatic neuroendocrine tumors (GEP-NET) and correlate them with tumor malignancy and progression. LAT-1, GLUT-1, and pVHL expression was analyzed in 116 GEP-NETs and 48 peritumoral tissue samples by immunohistochemistry. LAT-1 was stably silenced using specific shRNA in the human NET BON cell line. LAT-1 expression was significantly increased in tumor tissue compared to non-tumor tissue in both gastrointestinal (67% vs. 44%) and pancreatic NETs (54% vs. 31%). Similarly, GLUT-1 was substantially elevated in gastrointestinal (74% vs. 19%) and pancreatic (58% vs. 4%) NETs. In contrast, pVHL expression was decreased (85% vs. 58%) in pancreatic NETs. Tumors with metastases at diagnosis displayed increased LAT-1 and GLUT-1 and decreased pVHL expression (p < 0.001). In accordance with these data, silencing LAT-1 curtailed cell proliferation in BON cells. These findings suggest that specific mechanisms that increase nutrient uptake, such as LAT-1 and GLUT-1, are increased in GEP-NETs, whereas pVHL is decreased. These markers might be related to the proliferation and metastatic capacity of these tumorseng© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Neuroendocrine tumorsLAT-1GLUT-1BiomarkerGastroenteropancreatic neuroendocrine tumorsjournal article10.3390/cancers121029682072-6694open access