The role of Snail in prostate cancer

Abstract

hairpin RNA; VEGF-A, vascular endothelial growth factor-A; NRP1, neuropilin-1; GDF-9, growth and differentiation factor 9; HIF-1a, hypoxia inducible factor 1 a; ERβ1, estrogen receptor β-1; NED, neuroendocrine differentiation; RANKL, receptor activator of NFkB ligand; ROS, reactive oxygen species; GA, gambogic acid; EGCG, epigallocatechin-3-gallate; PTL, sesquiterpene lactone parthenolideProstate cancer is the second most frequently diagnosed cancer and the sixth leading cause of death from cancer in men. Epithelial-mesenchymal transition (EMT) is a process by which cancer cells invade and migrate, and is characterized by loss of cell-cell adhesion molecules such as E-cadherin and increased expression of mesenchymal proteins such as vimentin; EMT is also associated with resistance to therapy. Snail, a master regulator of EMT, has been extensively studied and reported in cancers such as breast and colon; however, its role in prostate cancer is not as widely reported. The purpose of this review is to put together recent facts that summarize Snail signaling in human prostate cancer. Snail is overexpressed in prostate cancer and its expression and activity is controlled via phosphorylation and growth factor signaling. Snail is involved in its canonical role of inducing EMT in prostate cancer cells; however, it plays a role in non-canonical pathways that do not involve EMT such regulation of bone turnover and neuroendocrine differentiation. Thus, studies indicate that Snail signaling contributes to prostate cancer progression and metastasis and therapeutic targeting of Snail in prostate cancer holds promise in future.

Paeoniflorin suppresses TGF-β mediated epithelial-mesenchymal transition in pulmonary fibrosis through a Smad-dependent pathway

“…GAPDH was used as the internal control. [15] . EMT can be classified into three subtypes based on the situation under which it occurs.…”

Role of Epithelial Mesenchymal Transition in Prostate Tumorigenesis

“…The main function of these EMT related transcription factors is to repress the expression of epithelial associated genes and induction of mesenchymal genes [109]. The information related to the functions and molecular targets of the established TFs in PCa is well known and has been reviewed extensively [43, 110, 111]. Here, we focus more on some of the newly identified TFs like YB-1, p63, OVOL family and their role during EMT in PCa.…”

Transición epitelial-mesenquimal en la progresión del adenocarcinoma prostático

“…Su efecto es aumentar la migración y la invasión, lo que refuerza el papel central que juega la pérdida de la E-cadherina en el proceso de la EMT (21,29,44) que, a su vez, promueve la señalización de Wnt y se asocia con un nivel alto de Snail en el núcleo (21,45). La actividad de Snail es controlada por la acción de varias quinasas, y su fosforilación por la glucógeno-sintasaquinasa (GSK-3β) promueve su traslado del núcleo al citosol donde es degradado, mientras que su fosforilación por la quinasa activada p21 (PAK1) y la proteína quinasa D1 (PKD1) induce su acumulación en el nú-cleo donde tiene función represora (7,29).…”

“…La actividad de Snail es controlada por la acción de varias quinasas, y su fosforilación por la glucógeno-sintasaquinasa (GSK-3β) promueve su traslado del núcleo al citosol donde es degradado, mientras que su fosforilación por la quinasa activada p21 (PAK1) y la proteína quinasa D1 (PKD1) induce su acumulación en el nú-cleo donde tiene función represora (7,29).…”

“…Este además participa en la inducción de la EMT en respuesta a la hipoxia (48,49). También se ha encontrado sobreexpresión de Snail en el CaP, con aumento progresivo desde el tejido benigno hasta las metástasis, asociado con índice alto de Gleason y mal pronóstico (29,32,50).…”