RT Journal Article
T1 Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer.
A1 Gomez-Gomez, Enrique
A1 Jimenez-Vacas, Juan M.
A1 Pedraza-Arevalo, Sergio
A1 Lopez-Lopez, Fernando
A1 Herrero-Aguayo, Vicente
A1 Hormaechea-Agulla, Daniel
A1 Valero-Rosa, Jose
A1 Ibañez-Costa, Alejandro
A1 Leon-Gonzalez, Antonio J.
A1 Sanchez-Sanchez, Rafael
A1 Gonzalez-Serrano, Teresa
A1 Requena-Tapia, Maria J.
A1 Castaño, Justo P.
A1 Carrasco-Valiente, Julia
A1 Gahete, Manuel D.
A1 Luque, Raul M.
K1 Aggressiveness
K1 Biomarker
K1 Engrailed homeobox variants
K1 Prostate cancer
AB Engrailed variant-2 (EN2) has been suggested as a potential diagnostic biomarker; however, its presence and functional role in prostate cancer (PCa) cells is still controversial or unknown. Here, we analyzed 1) the expression/secretion profile of EN2 in five independent samples cohorts from PCa patients and controls (prostate tissues and/or urine) to determine its utility as a PCa biomarker; and 2) the functional role of EN2 in normal (RWPE1) and tumor (LNCaP/22Rv1/PC3) prostate cells to explore its potential value as therapeutic target. EN2 was overexpressed in our two cohorts of PCa tissues compared to control and in tumor cell lines compared with normal-like prostate cells. This profile was corroborated in silico in three independent data sets [The Cancer Genome Atlas(TCGA)/Memorial Sloan Kettering Cancer Center (MSKCC)/Grasso]. Consistently, urine EN2 levels were elevated and enabled discrimination between PCa and control patients. EN2 treatment increased cell proliferation in LNCaP/22Rv1/PC3 cells, migration in RWPE1/PC3 cells, and PSA secretion in LNCaP cells. These effects were associated, at least in the androgen-sensitive LNCaP cells, with increased AKT and androgen-receptor phosphorylation levels and with modulation of key cancer-associated genes. Consistently, EN2 treatment also regulated androgen-receptor activity (full-length and splicing variants) in androgen-sensitive 22Rv1 cells. Altogether, this study demonstrates the potential utility of EN2 as a non-invasive diagnostic biomarker for PCa and provides novel and valuable information to further investigate its putative utility to develop new therapeutic tools in PCa.
PB MDPI
SN 2077-0383
YR 2019
FD 2019-09-02
LK http://hdl.handle.net/10668/14483
UL http://hdl.handle.net/10668/14483
LA en
NO Gómez-Gómez E, Jiménez-Vacas JM, Pedraza-Arévalo S, López-López F, Herrero-Aguayo V, Hormaechea-Agulla D, et al. Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer. J Clin Med. 2019 Sep 6;8(9):1400
DS RISalud
RD Apr 7, 2025