SNAI2/Slug gene is silenced in prostate cancer and regulates neuroendocrine differentiation, metastasis-suppressor and pluripotency gene expression

Silvia Esposito, Marco V. Russo, Irma Airoldi, Maria Grazia Tupone, Carlo Sorrentino, Giulia Barbarito, Serena Di Meo, Emma Di Carlo

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Prostate Cancer (PCa)-related deaths are mostly due to metastasization of poorly differentiated adenocarcinomas often endowed with neuroendocrine differentiation (NED) areas. The SNAI2/Slug gene is a major regulator of cell migration and tumor metastasization. We here assessed its biological significance in NED, and metastatic potential of PCa. SNAI2 expression was down-regulated in most PCa epithelia, in association with gene promoter methylation, except for cell clusters forming: a. the expansion/invasion front of high-grade PCa, b. NED areas, or c. lymph node metastasis. Knockdown of SNAI2 in PC3 cells down-regulated the expression of neuraltissue- associated adhesion molecules, Neural-Cadherin, Neural-Cadherin-2, Neuronal- Cell-Adhesion-Molecule, and of the NED marker Neuron-Specific Enolase, whereas it abolished Chromogranin-A expression. The metastasis-suppressor genes, Nm23-H1 and KISS1, were up-regulated, while the pluripotency genes SOX2, NOTCH1, CD44v6, WWTR1/TAZ and YAP1 were dramatically down-regulated. Over-expression of SNAI2 in DU145 cells substantiated its ability to regulate metastasis-suppressor, NED and pluripotency genes. In PCa and lymph node metastasis, expression of SOX2 and NOTCH1 was highly related to that of SNAI2. In conclusion, I. SNAI2 silencing in PCa may turn-off the expression of NED markers and pluripotency genes, while turning-on that of specific metastasissuppressors, II. SNAI2 expression in selected PCa cells, by regulating their self-renewal, NED and metastatic potential, endows them with highly malignant properties. SNAI2 may thus constitute a key target for modern approaches to PCa progression.

Original languageEnglish
Pages (from-to)17121-17134
Number of pages14
JournalOncotarget
Volume6
Issue number19
Publication statusPublished - 2015

Fingerprint

Gastropoda
Tumor Suppressor Genes
Prostatic Neoplasms
Gene Expression
Genes
Cadherins
Differentiation Antigens
Neoplasm Metastasis
Neuronal Cell Adhesion Molecules
Lymph Nodes
Chromogranin A
Phosphopyruvate Hydratase
Methylation
Cell Movement
Adenocarcinoma
Epithelium

Keywords

  • Laser capture microdissection
  • Neuroendocrine differentiation
  • Prostate cancer
  • SNAI2/Slug

ASJC Scopus subject areas

  • Oncology

Cite this

Esposito, S., Russo, M. V., Airoldi, I., Tupone, M. G., Sorrentino, C., Barbarito, G., ... Carlo, E. D. (2015). SNAI2/Slug gene is silenced in prostate cancer and regulates neuroendocrine differentiation, metastasis-suppressor and pluripotency gene expression. Oncotarget, 6(19), 17121-17134.

SNAI2/Slug gene is silenced in prostate cancer and regulates neuroendocrine differentiation, metastasis-suppressor and pluripotency gene expression. / Esposito, Silvia; Russo, Marco V.; Airoldi, Irma; Tupone, Maria Grazia; Sorrentino, Carlo; Barbarito, Giulia; Meo, Serena Di; Carlo, Emma Di.

In: Oncotarget, Vol. 6, No. 19, 2015, p. 17121-17134.

Research output: Contribution to journalArticle

Esposito, S, Russo, MV, Airoldi, I, Tupone, MG, Sorrentino, C, Barbarito, G, Meo, SD & Carlo, ED 2015, 'SNAI2/Slug gene is silenced in prostate cancer and regulates neuroendocrine differentiation, metastasis-suppressor and pluripotency gene expression', Oncotarget, vol. 6, no. 19, pp. 17121-17134.
Esposito, Silvia ; Russo, Marco V. ; Airoldi, Irma ; Tupone, Maria Grazia ; Sorrentino, Carlo ; Barbarito, Giulia ; Meo, Serena Di ; Carlo, Emma Di. / SNAI2/Slug gene is silenced in prostate cancer and regulates neuroendocrine differentiation, metastasis-suppressor and pluripotency gene expression. In: Oncotarget. 2015 ; Vol. 6, No. 19. pp. 17121-17134.
@article{307ba7cbe84f4a5189b875a159822270,
title = "SNAI2/Slug gene is silenced in prostate cancer and regulates neuroendocrine differentiation, metastasis-suppressor and pluripotency gene expression",
abstract = "Prostate Cancer (PCa)-related deaths are mostly due to metastasization of poorly differentiated adenocarcinomas often endowed with neuroendocrine differentiation (NED) areas. The SNAI2/Slug gene is a major regulator of cell migration and tumor metastasization. We here assessed its biological significance in NED, and metastatic potential of PCa. SNAI2 expression was down-regulated in most PCa epithelia, in association with gene promoter methylation, except for cell clusters forming: a. the expansion/invasion front of high-grade PCa, b. NED areas, or c. lymph node metastasis. Knockdown of SNAI2 in PC3 cells down-regulated the expression of neuraltissue- associated adhesion molecules, Neural-Cadherin, Neural-Cadherin-2, Neuronal- Cell-Adhesion-Molecule, and of the NED marker Neuron-Specific Enolase, whereas it abolished Chromogranin-A expression. The metastasis-suppressor genes, Nm23-H1 and KISS1, were up-regulated, while the pluripotency genes SOX2, NOTCH1, CD44v6, WWTR1/TAZ and YAP1 were dramatically down-regulated. Over-expression of SNAI2 in DU145 cells substantiated its ability to regulate metastasis-suppressor, NED and pluripotency genes. In PCa and lymph node metastasis, expression of SOX2 and NOTCH1 was highly related to that of SNAI2. In conclusion, I. SNAI2 silencing in PCa may turn-off the expression of NED markers and pluripotency genes, while turning-on that of specific metastasissuppressors, II. SNAI2 expression in selected PCa cells, by regulating their self-renewal, NED and metastatic potential, endows them with highly malignant properties. SNAI2 may thus constitute a key target for modern approaches to PCa progression.",
keywords = "Laser capture microdissection, Neuroendocrine differentiation, Prostate cancer, SNAI2/Slug",
author = "Silvia Esposito and Russo, {Marco V.} and Irma Airoldi and Tupone, {Maria Grazia} and Carlo Sorrentino and Giulia Barbarito and Meo, {Serena Di} and Carlo, {Emma Di}",
year = "2015",
language = "English",
volume = "6",
pages = "17121--17134",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "19",

}

TY - JOUR

T1 - SNAI2/Slug gene is silenced in prostate cancer and regulates neuroendocrine differentiation, metastasis-suppressor and pluripotency gene expression

AU - Esposito, Silvia

AU - Russo, Marco V.

AU - Airoldi, Irma

AU - Tupone, Maria Grazia

AU - Sorrentino, Carlo

AU - Barbarito, Giulia

AU - Meo, Serena Di

AU - Carlo, Emma Di

PY - 2015

Y1 - 2015

N2 - Prostate Cancer (PCa)-related deaths are mostly due to metastasization of poorly differentiated adenocarcinomas often endowed with neuroendocrine differentiation (NED) areas. The SNAI2/Slug gene is a major regulator of cell migration and tumor metastasization. We here assessed its biological significance in NED, and metastatic potential of PCa. SNAI2 expression was down-regulated in most PCa epithelia, in association with gene promoter methylation, except for cell clusters forming: a. the expansion/invasion front of high-grade PCa, b. NED areas, or c. lymph node metastasis. Knockdown of SNAI2 in PC3 cells down-regulated the expression of neuraltissue- associated adhesion molecules, Neural-Cadherin, Neural-Cadherin-2, Neuronal- Cell-Adhesion-Molecule, and of the NED marker Neuron-Specific Enolase, whereas it abolished Chromogranin-A expression. The metastasis-suppressor genes, Nm23-H1 and KISS1, were up-regulated, while the pluripotency genes SOX2, NOTCH1, CD44v6, WWTR1/TAZ and YAP1 were dramatically down-regulated. Over-expression of SNAI2 in DU145 cells substantiated its ability to regulate metastasis-suppressor, NED and pluripotency genes. In PCa and lymph node metastasis, expression of SOX2 and NOTCH1 was highly related to that of SNAI2. In conclusion, I. SNAI2 silencing in PCa may turn-off the expression of NED markers and pluripotency genes, while turning-on that of specific metastasissuppressors, II. SNAI2 expression in selected PCa cells, by regulating their self-renewal, NED and metastatic potential, endows them with highly malignant properties. SNAI2 may thus constitute a key target for modern approaches to PCa progression.

AB - Prostate Cancer (PCa)-related deaths are mostly due to metastasization of poorly differentiated adenocarcinomas often endowed with neuroendocrine differentiation (NED) areas. The SNAI2/Slug gene is a major regulator of cell migration and tumor metastasization. We here assessed its biological significance in NED, and metastatic potential of PCa. SNAI2 expression was down-regulated in most PCa epithelia, in association with gene promoter methylation, except for cell clusters forming: a. the expansion/invasion front of high-grade PCa, b. NED areas, or c. lymph node metastasis. Knockdown of SNAI2 in PC3 cells down-regulated the expression of neuraltissue- associated adhesion molecules, Neural-Cadherin, Neural-Cadherin-2, Neuronal- Cell-Adhesion-Molecule, and of the NED marker Neuron-Specific Enolase, whereas it abolished Chromogranin-A expression. The metastasis-suppressor genes, Nm23-H1 and KISS1, were up-regulated, while the pluripotency genes SOX2, NOTCH1, CD44v6, WWTR1/TAZ and YAP1 were dramatically down-regulated. Over-expression of SNAI2 in DU145 cells substantiated its ability to regulate metastasis-suppressor, NED and pluripotency genes. In PCa and lymph node metastasis, expression of SOX2 and NOTCH1 was highly related to that of SNAI2. In conclusion, I. SNAI2 silencing in PCa may turn-off the expression of NED markers and pluripotency genes, while turning-on that of specific metastasissuppressors, II. SNAI2 expression in selected PCa cells, by regulating their self-renewal, NED and metastatic potential, endows them with highly malignant properties. SNAI2 may thus constitute a key target for modern approaches to PCa progression.

KW - Laser capture microdissection

KW - Neuroendocrine differentiation

KW - Prostate cancer

KW - SNAI2/Slug

UR - http://www.scopus.com/inward/record.url?scp=84938245254&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938245254&partnerID=8YFLogxK

M3 - Article

VL - 6

SP - 17121

EP - 17134

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 19

ER -