scholarly journals Targeting Src-mediated Tyr216 phosphorylation and activation of GSK-3 in prostate cancer cells inhibit prostate cancer progression in vitro and in vivo

Oncotarget ◽  
2014 ◽  
Vol 5 (3) ◽  
pp. 775-787 ◽  
Author(s):  
Anna Goc ◽  
Belal Al-Husein ◽  
Katerina Katsanevas ◽  
Alison Steinbach ◽  
Uvette Lou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Prostate Cancer Cells

scholarly journals EZH2-TROAP Pathway Promotes Prostate Cancer Progression Via TWIST Signals

2021 ◽  
Vol 10 ◽  
Author(s):  
Lu Jin ◽  
Yibin Zhou ◽  
Guangqiang Chen ◽  
Guangcheng Dai ◽  
Kai Fu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Migration And Invasion ◽  
Prostate Cancer Progression ◽  
Prostate Cancer Cells ◽  
Normal Tissues ◽  
Phase Cycle ◽  
Prostate Cancer Treatments

Trophinin-associated protein (TROAP) has been shown to be overexpressed and promotes tumor progression in some tumors. We performed this study to assess the biological and clinical significance of TROAP in prostate cancer. We downloaded TROAP mRNA expression data from TCGA and GEO databases. We analyzed expressions of TROAP and other genes in prostate cancer tumors at different stages and assessed Gleason scores. We used Celigo image, Transwell, and rescue assays, and flow cytometry detection to assess growth, apoptosis, proliferation, migration, and invasion of the prostate cancer cells. We identified and validated up- and down-stream genes in the TROAP pathway. The mRNA data suggested that TROAP expression was markedly upregulated in prostate cancer compared with its expression in normal tissues, especially in cancers with high stages and Gleason scores. Moreover, a high TROAP expression was associated with poor patient survival. Results of our in vitro assay showed that TROAP knockdown inhibited DU145 and PC3 cell proliferation and viability via cell apoptosis and S phase cycle arrest. The Transwell assay showed that TROAP knockdown inhibited cell migration and invasion, probably through MMP-9 and E-Cadherin modulation. Overexpression of TWIST partially abrogated the inhibitory effects of TROAP knockdown on prostate cancer cells. Our integrative mechanism dissection revealed that TROAP is in a pathway downstream of EZH2 and that it activates the TWIST/c-Myc pathway to regulate prostate cancer progression. In all, we identified TROAP as a driver of prostate cancer development and progression, providing a novel target for prostate cancer treatments.

scholarly journals Characterisation of the androgen regulation of glycine N-methyltransferase in prostate cancer cells

2013 ◽  
Vol 51 (3) ◽  
pp. 301-312 ◽  
Author(s):  
Silvia Ottaviani ◽  
Greg N Brooke ◽  
Ciara O'Hanlon-Brown ◽  
Jonathan Waxman ◽  
Simak Ali ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Regulatory Element ◽  
Prostate Cancer Cells ◽  
Protein Levels ◽  
Prostate Cancer Development ◽  
Androgen Regulation

The development and growth of prostate cancer is dependent on androgens; thus, the identification of androgen-regulated genes in prostate cancer cells is vital for defining the mechanisms of prostate cancer development and progression and developing new markers and targets for prostate cancer treatment. GlycineN-methyltransferase (GNMT) is aS-adenosylmethionine-dependent methyltransferase that has been recently identified as a novel androgen-regulated gene in prostate cancer cells. Although the importance of this protein in prostate cancer progression has been extensively addressed, little is known about the mechanism of its androgen regulation. Here, we show that GNMT expression is stimulated by androgen in androgen receptor (AR) expressing cells and that the stimulation occurs at the mRNA and protein levels. We have identified an androgen response element within the first exon of theGNMTgene and demonstrated that AR binds to this elementin vitroandin vivo. Together, these studies identify GNMT as a direct transcriptional target of the AR. As this is an evolutionarily conserved regulatory element, this highlights androgen regulation as an important feature of GNMT regulation.

scholarly journals Acetyl-L-Carnitine downregulates invasion (CXCR4/CXCL12, MMP-9) and angiogenesis (VEGF, CXCL8) pathways in prostate cancer cells: rationale for prevention and interception strategies

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Denisa Baci ◽  
Antonino Bruno ◽  
Caterina Cascini ◽  
Matteo Gallazzi ◽  
Lorenzo Mortara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Dietary Supplements ◽  
Cell Lines ◽  
Angiogenic Factors ◽  
Migration And Invasion ◽  
Prostate Cancer Cells

Abstract Background Prostate cancer (PCa) is a leading cause of cancer-related death in males worldwide. Exacerbated inflammation and angiogenesis have been largely demonstrated to contribute to PCa progression. Diverse naturally occurring compounds and dietary supplements are endowed with anti-oxidant, anti-inflammatory and anti-angiogenic activities, representing valid compounds to target the aberrant cytokine/chemokine production governing PCa progression and angiogenesis, in a chemopreventive setting. Using mass spectrometry analysis on serum samples of prostate cancer patients, we have previously found higher levels of carnitines in non-cancer individuals, suggesting a protective role. Here we investigated the ability of Acetyl-L-carnitine (ALCAR) to interfere with key functional properties of prostate cancer progression and angiogenesis in vitro and in vivo and identified target molecules modulated by ALCAR. Methods The chemopreventive/angiopreventive activities ALCAR were investigated in vitro on four different prostate cancer (PCa) cell lines (PC-3, DU-145, LNCaP, 22Rv1) and a benign prostatic hyperplasia (BPH) cell line. The effects of ALCAR on the induction of apoptosis and cell cycle arrest were investigated by flow cytometry (FC). Functional analysis of cell adhesion, migration and invasion (Boyden chambers) were performed. ALCAR modulation of surface antigen receptor (chemokines) and intracellular cytokine production was assessed by FC. The release of pro-angiogenic factors was detected by a multiplex immunoassay. The effects of ALCAR on PCa cell growth in vivo was investigated using tumour xenografts. Results We found that ALCAR reduces cell proliferation, induces apoptosis, hinders the production of pro inflammatory cytokines (TNF-α and IFN-γ) and of chemokines CCL2, CXCL12 and receptor CXCR4 involved in the chemotactic axis and impairs the adhesion, migration and invasion capabilities of PCa and BPH cells in vitro. ALCAR exerts angiopreventive activities on PCa by reducing production/release of pro angiogenic factors (VEGF, CXCL8, CCL2, angiogenin) and metalloprotease MMP-9. Exposure of endothelial cells to conditioned media from PCa cells, pre-treated with ALCAR, inhibited the expression of CXCR4, CXCR1, CXCR2 and CCR2 compared to those from untreated cells. Oral administration (drinking water) of ALCAR to mice xenografted with two different PCa cell lines, resulted in reduced tumour cell growth in vivo. Conclusions Our results highlight the capability of ALCAR to down-modulate growth, adhesion, migration and invasion of prostate cancer cells, by reducing the production of several crucial chemokines, cytokines and MMP9. ALCAR is a widely diffused dietary supplements and our findings provide a rational for studying ALCAR as a possible molecule for chemoprevention approaches in subjects at high risk to develop prostate cancer. We propose ALCAR as a new possible “repurposed agent’ for cancer prevention and interception, similar to aspirin, metformin or beta-blockers.

787 SHARED LIPID ENERGY: PROSTATE CANCER CELLS STIMULATE ADIPOCYTE MIGRATION IN VITRO AND IN VIVO

2013 ◽  
Vol 189 (4S) ◽  
Author(s):  
Kristian Novakovic ◽  
Margo Quinn ◽  
Philip Fitchev ◽  
Mona Cornwell ◽  
Charles Brendler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Prostate Cancer Cells
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