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Open AccessArticle

Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer

1
Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Córdoba, Spain
2
Department of Cell Biology, Physiology, and Immunology, Universidad de Córdoba, 14004 Córdoba, Spain
3
Reina Sofia University Hospital, 14004 Córdoba, Spain
4
Urology Service, Reina Sofia University Hospital, 14004 Córdoba, Spain
5
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 14004 Córdoba, Spain
6
Anatomical Pathology Service, Reina Sofia University Hospital, 14004 Córdoba, Spain
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(9), 1400; https://doi.org/10.3390/jcm8091400
Received: 20 August 2019 / Revised: 29 August 2019 / Accepted: 2 September 2019 / Published: 6 September 2019
(This article belongs to the Special Issue Targeting the Androgen Receptor for Treatment of Prostate Cancer)
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. View Full-Text
Keywords: engrailed homeobox variants; prostate cancer; aggressiveness; biomarker engrailed homeobox variants; prostate cancer; aggressiveness; biomarker
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E., G.-G.; J. M., J.-V.; S., P.-A.; F., L.-L.; V., H.-A.; D., H.-A.; J., V.-R.; A., I.-C.; J., L.-G.A.; R., S.-S.; T., G.-S.; M. J., R.-T.; J. P., C.; J., C.-V.; M. D., G.; R. M., L. Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer. J. Clin. Med. 2019, 8, 1400.

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