SNAIL transcription factor increases the motility and invasive capacity of prostate cancer cells

Abstract

The incidence and mortality rates of prostate cancer (PCa) are increasing, and PCa is almost the second-leading cause of cancer-associated mortality in men. During tumor progression, epithelial cells decrease the number of adhesion molecules, change their polarity and position, rearrange their cytoskeleton and increase their migratory and invasive capacities. These changes are known under the concept of epithelial-mesenchymal transition (EMT). EMT is characterized by an upregulation of certain transcription factors, including SNAIL1, which represses genes that are characteristic of an epithelial phenotype, including E-cadherin, and indirectly increase the expression levels of genes, which are associated with the mesenchymal phenotype. It has been suggested that the transcription factor, SNAIL1, decreases the proliferation and increases the migratory and invasive capacities of PCa cell lines. The present study was performed using LNCaP and PC3 cell lines, in which the expression levels of SNAIL1 were increased or silenced through the use of lentiviral vectors. The expression levels of EMT markers were quantified using reverse transcription-quantitative polymerase chain reaction and western blot analysis. In addition, cell survival was analyzed using an MTS assay; cell proliferation was examined using an antibody targeting Ki-67; migration on plates with 8 µm pores to allow the passage of cells; and invasiveness was analyzed using a membrane chamber covered in dried basement membrane matrix solution. The levels of apoptosis were determined using a Caspase 3/7 assay containing a substrate modified by caspases 3 and 7. The results demonstrated that the overexpression and silencing of SNAIL1 decreased cell proliferation and survival. However, the overexpression of SNAIL1 decreased apoptosis, compared with cells with the SNAIL1-silenced cells, in which cell apoptosis increased. The migration and invasive capacities increased in the cells overexpressing SNAIL1, and decreased when SNAIL1 was silenced. In conclusion, PCa cells overexpressing SNAIL1 exhibited characteristics of an EMT phenotype, whereas the silencing of the SNAIL1 transcriptional repressor promoted an epithelial-like phenotype, with decreased migration and invasion, characteristic of mesenchymal cells.

Inflammatory mediators of prostate epithelial cells stimulated with Trichomonas vaginalis promote proliferative and invasive properties of prostate cancer cells

“…An important characteristic of EMT is the loss of expression of epithelial cell markers and the development of a mesenchymal phenotype by increasing mesenchymal markers, such as snail1, snail2, and α‐SMA . Recently, several studies have indicated that EMT progression is regulated by activation of snail signaling in various cancer cell lines including prostate and breast cancer cells . We showed above that inflammatory mediators, such as CCL2, IL‐6, CXCL8, and PGE2, produced by Tv stimulation of prostate epithelial cells induced EMT of PCa cells through the receptors of these inflammatory mediators.…”

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

“…Among them, Snail1 and Snail2 are activated in the EMT during development, fibrosis, and cancer. The upregulation of Snail1 is found in many different types of cancer such as gastric, colorectal, and prostate cancer . In addition, the overexpression of Snail1 enhanced the motility and invasion of prostate cancer cells, and the silencing of Snail remarkedly suppressed the adhesion, migration, and invasion of Hep‐2 cells .…”

“…Recently, it was reported that toosendanin significantly inhibited TGF‐β1‐induced EMT in lung cancer cells via the extracellular signal‐regulated kinase (ERK)/Snail pathway and suppressed EMT and tumor growth in pancreatic cancer by deactivating the RAC‐α serine/threonine‐protein kinase (Akt)/mechanistic target of rapamycin (mTOR) pathway (Figure ), which suggests that toosendanin is a promising pharmacological agent for the treatment of cancer . A recent study revealed that neferine enhanced oxaliplatin sensitivity by inhibiting EMT via the Snail pathway . In addition, ponicidin is a major diterpenoid compound extracted from Rabdosia rubescens (Hemsl.)…”

“…The upregulation of Snail1 is found in many different types of cancer such as gastric, colorectal, and prostate cancer . In addition, the overexpression of Snail1 enhanced the motility and invasion of prostate cancer cells, and the silencing of Snail remarkedly suppressed the adhesion, migration, and invasion of Hep‐2 cells . Further study revealed that the knockdown of Snail blocked the EMT, which was accompanied by the downregulation of the expression of MMP‐2, MMP‐9, vimentin, N‐cadherin, and fibronectin .…”

“…In addition, the overexpression of Snail1 enhanced the motility and invasion of prostate cancer cells, and the silencing of Snail remarkedly suppressed the adhesion, migration, and invasion of Hep‐2 cells . Further study revealed that the knockdown of Snail blocked the EMT, which was accompanied by the downregulation of the expression of MMP‐2, MMP‐9, vimentin, N‐cadherin, and fibronectin . Moreover, Snail expression was demonstrated at different stages of kidney fibrosis, and the reactivation of Snail‐induced renal fibrosis (Figure ).…”