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Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality
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Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality
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Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality
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Journal Article
Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality
2017
Overview
Recent evidence has implicated the transmembrane co-receptor neuropilin-1 (NRP1) in cancer progression. Primarily known as a regulator of neuronal guidance and angiogenesis, NRP1 is also expressed in multiple human malignancies, where it promotes tumor angiogenesis. However, non-angiogenic roles of NRP1 in tumor progression remain poorly characterized. In this study, we define
NRP1
as an androgen-repressed gene whose expression is elevated during the adaptation of prostate tumors to androgen-targeted therapies (ATTs), and subsequent progression to metastatic castration-resistant prostate cancer (mCRPC). Using short hairpin RNA (shRNA)-mediated suppression of
NRP1
, we demonstrate that NRP1 regulates the mesenchymal phenotype of mCRPC cell models and the invasive and metastatic dissemination of tumor cells
in vivo
. In patients, immunohistochemical staining of tissue microarrays and mRNA expression analyses revealed a positive association between NRP1 expression and increasing Gleason grade, pathological T score, positive lymph node status and primary therapy failure. Furthermore, multivariate analysis of several large clinical prostate cancer (PCa) cohorts identified
NRP1
expression at radical prostatectomy as an independent prognostic biomarker of biochemical recurrence after radiation therapy, metastasis and cancer-specific mortality. This study identifies
NRP1
for the first time as a novel androgen-suppressed gene upregulated during the adaptive response of prostate tumors to ATTs and a prognostic biomarker of clinical metastasis and lethal PCa.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 38/39
/ 38/89
/ 38/91
/ 42/41
/ 64/116
/ 82/51
/ 82/80
/ Androgen Antagonists - therapeutic use
/ Cancer
/ Epithelial-Mesenchymal Transition
/ Gene Expression Regulation, Neoplastic - drug effects
/ Humans
/ Lymph
/ Male
/ Medicine
/ Neurons
/ Oncology
/ Original
/ Prostatic Neoplasms - drug therapy
/ Prostatic Neoplasms - genetics
/ Prostatic Neoplasms - mortality
/ Prostatic Neoplasms, Castration-Resistant - mortality
/ Tumors
