scholarly journals Estrogen receptor β2 and β5 are associated with poor prognosis in prostate cancer, and promote cancer cell migration and invasion

2010 ◽  
Vol 17 (3) ◽  
pp. 675-689 ◽  
Author(s):  
Yuet-Kin Leung ◽  
Hung-Ming Lam ◽  
Shulin Wu ◽  
Dan Song ◽  
Linda Levin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Specific Antigen ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Independent Prognostic Marker ◽  
Prostate Carcinogenesis ◽  
Kaplan Meier ◽  
Cell Invasiveness

Estrogens play a pivotal role in the development and progression of prostate cancer (PCa). Their actions are mediated by estrogen receptors (ERs), particularly ERβ in the prostate epithelium. With the discovery of ERβ isoforms, data from previous studies that focused principally on the wild-type ERβ (ERβ1) may not be adequate in explaining the still controversial role of ERβ(s) in prostate carcinogenesis. In this study, using newly generated isoform-specific antibodies, immunohistochemistry (IHC) was performed on a tumor microarray comprised of 144 specimens. IHC results were correlated with pathological and clinical follow-up data to delineate the distinct roles of ERβ1, ERβ2, and ERβ5 in PCa. ERβ2 was commonly found in the cytoplasm and was the most abundant isoform followed by ERβ1 localized predominantly in the nucleus, and ERβ5 was primarily located in the cytoplasm. Logistic regression analyses demonstrated that nuclear ERβ2 (nERβ2) is an independent prognostic marker for prostate specific antigen (PSA) failure and postoperative metastasis (POM). In a Kaplan–Meier analysis, the combined expression of both nERβ2 and cytoplasmic ERβ5 identified a group of patients with the shortest POM-free survival. Cox proportional hazard models revealed that nERβ2 predicted shorter time to POM. In concordance with IHC data, stable, ectopic expression of ERβ2 or ERβ5 enhanced PCa cell invasiveness but only PCa cells expressing ERβ5 exhibited augmented cell migration. This is the first study to uncover a metastasis-promoting role of ERβ2 and ERβ5 in PCa, and show that the two isoforms, singularly and conjointly, have prognostic values for PCa progression. These findings may aid future clinical management of PCa.

scholarly journals Expression and Functional Role of CCR9 in Prostate Cancer Cell Migration and Invasion

2004 ◽  
Vol 10 (24) ◽  
pp. 8743-8750 ◽  
Author(s):  
Shailesh Singh ◽  
Udai P. Singh ◽  
Jonathan K. Stiles ◽  
William E. Grizzle ◽  
James W. Lillard
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Functional Role ◽  
Prostate Cancer Cell ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Cell Migration And Invasion

scholarly journals Xanthine Oxidase/Dehydrogenase Activity as a Source of Oxidative Stress in Prostate Cancer Tissue

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 668
Author(s):  
Andrej Veljković ◽  
Jovan Hadži-Dokić ◽  
Dušan Sokolović ◽  
Dragoslav Bašić ◽  
Ljubinka Veličković-Janković ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prostate Cancer ◽  
Xanthine Oxidase ◽  
Dehydrogenase Activity ◽  
Tumor Tissue ◽  
Specific Antigen ◽  
Cancer Tissue ◽  
Prostate Carcinogenesis ◽  
Promising Treatment

Prostate cancer (PC) is one of the most frequent malignancies. Better biomarkers are constantly wanted, such as those which can help with the prediction of cancer behavior. What is also needed is a marker which may serve as a possible therapeutic target. Oxidative stress (OS), which is a hallmark of cancer, is included in the pathogenesis and progression of PC. We have conducted the present study to determine whether xanthine oxidase/dehydrogenase activity is the source of OS in prostate tissue. We have also determined the concentration of TBA-reactive substances (TBARS) and advanced oxidation protein products (AOPP), as well as the activity of catalase. Xanthine oxidase (XO) activity is significantly higher (p < 0.001) in tumor tissue when compared to the control healthy tissue. The concentration of TBARS (p < 0.001) and AOPP (p < 0.05) are also higher in tumor tissue. Catalase has raised its activity (p < 0.05) versus the control. There is also a strong correlation between XO activity and prostate-specific antigen (PSA) levels in the serum. These results indicate a significant role of XO activity in OS in prostate carcinogenesis, and it could be a possible theranostic biomarker, which can be important for a better understanding of the disease, its evolution, and prognosis. A promising treatment may be using XO inhibitors such as allopurinol as adjuvant therapy.

scholarly journals Exosomes-Mediated Transfer of Itga2 Promotes Migration and Invasion of Prostate Cancer Cells by Inducing Epithelial-Mesenchymal Transition

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2300
Author(s):  
Rofaida Gaballa ◽  
Hamdy E. A. Ali ◽  
Mohamed O. Mahmoud ◽  
Johng S. Rhim ◽  
Hamed I. Ali ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Ectopic Expression ◽  
Normal Subjects ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Aggressive Phenotype ◽  
Endogenous Expression

Although integrin alpha 2 subunit (ITGA2) mediates cancer progression and metastasis, its transfer by exosomes has not been investigated in prostate cancer (PCa). We aimed to determine the role of exosomal ITGA2 derived from castration-resistant PCa (CRPC) cells in promoting aggressive phenotypes in androgen receptor (AR)-positive cells. Exosomes were co-incubated with recipient cells and tested for different cellular assays. ITGA2 was enriched in exosomes derived from CRPC cells. Co-culture of AR-positive cells with CRPC-derived exosomes increased their proliferation, migration, and invasion by promoting epithelial-mesenchymal transition, which was reversed via ITGA2 knockdown or inhibition of exosomal uptake by methyl-β-cyclodextrin (MβCD). Ectopic expression of ITGA2 reproduced the effect of exosomal ITGA2 in PCa cells. ITGA2 transferred by exosomes exerted its effect within a shorter time compared to that triggered by its endogenous expression. The difference of ITGA2 protein expression in localized tumors and those with lymph node metastatic tissues was indistinguishable. Nevertheless, its abundance was higher in circulating exosomes collected from PCa patients when compared with normal subjects. Our findings indicate the possible role of the exosomal-ITGA2 transfer in altering the phenotype of AR-positive cells towards more aggressive phenotype. Thus, interfering with exosomal cargo transfer may inhibit the development of aggressive phenotype in PCa cells.

E2F5 promotes prostate cancer cell migration and invasion through regulation of TFPI2, MMP-2 and MMP-9

2020 ◽  
Author(s):  
Deepmala Karmakar ◽  
Jyotirindra Maity ◽  
Payel Mondal ◽  
Puskar Shyam Chowdhury ◽  
Nilabja Sikdar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cellular Proliferation ◽  
Therapeutic Potential ◽  
Quantitative Polymerase Chain Reaction ◽  
Site Directed Mutagenesis ◽  
Migration And Invasion ◽  
Dual Function ◽  
Pc3 Cells

Abstract Previously, our laboratory demonstrated that a deregulated E2F5/p38/SMAD3 axis was associated with uncontrolled cellular proliferation in prostate cancer (PCa). Here, we investigate the role of E2F5 in PCa in further details. RNAi-mediated E2F5 knockdown and pathway-focused gene expression profiling in PC3 cells identified TFPI2 as a downstream target of E2F5. Manipulation of E2F5 expression was also found to alter MMP-2 and MMP-9 levels as detected by Proteome Profiler array, western blot and reverse transcription coupled quantitative polymerase chain reaction Site-directed mutagenesis, dual-luciferase assays and chromatin immunoprecipitation with anti-E2F5-IgG coupled with qPCR confirmed recruitment of E2F5 on TFPI2, MMP-2 and MMP-9 promoters. RNAi-mediated knockdown of E2F5 expression in PC3 caused a significant alteration of cell migration while that of TFFI2 resulted in a modest change. Abrogation of E2F5 and TFPI2 expression was associated with significant changes in the gelatinolytic activity of active forms of MMP-2 and MMP-9. Moreover, E2F5, MMP-2 and MMP-9 levels were elevated in biopsies of PCa patients relative to that of benign hyperplasia, while TFPI2 expression was reduced. MMP-9 was coimmunoprecipitated with anti-TFPI2-IgG in PCa tissue samples suggesting a direct interaction between the proteins. Finally, artemisinin treatment in PC3 cells repressed E2F5 along with MMP-2/MMP-9 while triggering TFPI2 expression which alleviated PC3 aggressiveness possibly through inhibition of MMP activities. Together, our study reinstates an oncogenic role of E2F5 which operates as a dual-function transcription factor for its targets TFPI2, MMP-2 and MMP-9 and promotes cellular invasiveness. This study also indicates a therapeutic potential of artemisinin, a natural compound which acts by correcting dysfunctional E2F5/TFPI2/MMP axis in PCa.

scholarly journals Identification of TRPV4 as a novel target in invasiveness of colorectal cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Peng Zhang ◽  
Jian Xu ◽  
Hua Zhang ◽  
Xiao-Yu Liu
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Critical Role ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Cancer Invasiveness ◽  
Cell Invasiveness ◽  
Novel Target ◽  
Local Metastasis

Abstract Background Emerging evidence has indicated the critical role of TRPV4 in diverse human cancers. However, the underlying molecular mechanism of TRPV4 in colon cancer invasiveness is still unknown. Methods Immunohistochemistry staining was used to analyze the expression of TRPV4 and ZEB1 in clinical tissues; Wound healing and transwell assays were applied to determine the cell invasiveness; Western blot was used to explore the relation between TRPV4 and ZEB1. Results Colon cancer cells were transfected with siRNA against TRPV4 or HC067047 (a selective TRPV4 antagonist), TRPV4 full-length plasmid or siRNA against ZEB1, or both, in order to measure cell migration and invasion. And we found that TRPV4 silencing or inhibition exhibited an inhibitory role in colon cancer cell migration and invasion, coupled with compromised EMT process, and suppressed AKT activity. TRPV4 stimulated expression of ZEB1 and consequently contributed to EMT process and invasiveness. It was also revealed that overexpression of TRPV4 and ZEB1 in clinical patients with local metastasis, and positive correlation between TRPV4 and ZEB1. Conclusions Our results uncovered the role of TRPV4 in tumor metastasis and highlighted the potential mechanism of TRPV4-ZEB1 axis in indicating EMT.

scholarly journals E2F2 inhibition induces autophagy to impair metastasis via the PI3K/Akt/mTOR pathway in gastric cancer

2020 ◽  
Author(s):  
Hui Li ◽  
Shufen Zhao ◽  
Liwei Shen ◽  
Peige Wang ◽  
Shihai Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cox Regression ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Kaplan Meier ◽  
Patient Prognosis ◽  
Public Datasets

Abstract Background: E2F2 is a member of the E2F family of transcription factors with important yet incompletely understood biological functions in cancer. In some cancer types, controversial tumor-promoting and tumor-suppressive roles of E2F2 have been reported. However, the biological role of E2F2 in gastric cancer (GC) remains to be determined. Methods: We analyzed E2F2 expression via multiple gene expression databases. The prognostic value of the E2F2 was determined by Kaplan-Meier Plotter and Cox regression. The correlations between E2F2 and cancer immune infiltrates were investigated via Tumor Immune Estimation Resource (TIMER). The functions and pathways of E2F2 and its 50 frequently changed genes closely associated with the family members were analyzed using Database for Annotation, Visualization, and Integrated Discovery (DAVID) software. We used immunohistochemistry (IHC), quantitative real-time PCR (qPCR) and western blot to verify the expression level of E2F2 in GC and further studied the effects of E2F2 on PI3K/Akt/mTOR activity; GC cell autophagy, migration, and invasion through wound healing assays, transwell assays, Western blotting, and transmission electron microscopy.Results: We observed that compared with normal gastric tissues/cells, E2F2 is highly expressed in gastric cancer tissues and cells in both the public datasets and in our experimental verification. High E2F2 expression was associated with poorer overall survival (OS). Moreover, E2F2 expression showed strong correlations with diverse immune marker sets in GC. Moreover, E2F2 overexpression promoted GC cell migration and invasion in vitro by inactivating PI3K/Akt/mTOR-mediated autophagy. Conversely, E2F2 inhibition suppressed GC cell migration and invasion in vitro by activating PI3K/Akt/mTOR-mediated autophagy.Conclusions: In conclusion, this study provides multi-level evidence for the importance of E2F2 in gastric carcinogenesis and its potential as a biomarker in GC. We demonstrated that E2F2 is overexpressed in GC and that high E2F2 expression is associated with aggressive tumor features and poorer patient prognosis. Further, our results suggest a potential novel immune regulatory role of E2F2 in tumor immunity. Functionally, we discovered a new role of E2F2 in regulating PI3K/Akt/mTOR-mediated autophagy and the downstream processes of cell migration and invasion. Our results could potentially reveal new targets and strategies for GC diagnosis and treatment.

The Role of Chromogranin A (CgA) in Monitoring Patients with Prostate Cancer Under Androgen Deprivation Therapy: Comparison with Prostatic Specific Antigen (PSA)

2008 ◽  
Vol 1 (2) ◽  
pp. 115-119
Author(s):  
Athanasios Bantis ◽  
Petros Sountoulides ◽  
Athanasios Zissimopoulos ◽  
Christos Kalaitzis ◽  
Stilianos Giannakopoulos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Chromogranin A ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Prostatic Specific Antigen

scholarly journals The role of microRNA-572 in the proliferation and chemotherapeutic treatment of prostate cancer

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110143
Author(s):  
Mingcui Zang ◽  
Xun Guo ◽  
Manqiu Chen
Keyword(s):  
Prostate Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Prostate Tumorigenesis ◽  
Expression Levels ◽  
Matrigel Invasion ◽  
Tensin Homolog ◽  
Docetaxel Treatment ◽  
Induced Apoptosis

Objective MicroRNAs (miRNAs) regulate prostate tumorigenesis and progression by involving different molecular pathways. In this study, we examined the role of miR-572 in prostate cancer (PCa). Methods The proliferation rates of LNCaP and PC-3 PCa cells were studied using MTT assays. Transwell migration and Matrigel invasion assays were performed to evaluate cell migration and invasion, respectively. Protein expression levels were examined using western blotting. Docetaxel-induced apoptosis was evaluated by Caspase-Glo3/7 assays. The putative miR-572 binding site in the phosphatase and tensin homolog (PTEN) 3ʹ untranslated region (3ʹ UTR) was assessed with dual-luciferase reporter assays. Additionally, miR-572 expression levels in human PCa tissues were examined by qRT-PCR assays. Results Upregulation of miR-572 promoted proliferation, migration, and invasion of PCa cells. Overexpression of miR-572 decreased sensitivity of PCa cells to docetaxel treatment by reducing docetaxel-induced apoptosis. MiR-572 can regulate migration and invasion in PCa cells. Furthermore, miR-572 could regulate expression of PTEN and p-AKT in PCa cells by directly binding to the PTEN 3ʹ UTR. MiR-572 expression levels were increased in human PCa tissues and associated with PCa stage. Conclusions miR-572 displayed essential roles in PCa tumor growth and its expression level may be used to predict docetaxel treatment in these tumors.

scholarly journals CDX2 and Reg IV expression and correlation in gastric cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dandan Chai ◽  
Huifen Du ◽  
Kesheng Li ◽  
Xueliang Zhang ◽  
Xiaoqin Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Real Time ◽  
Real Time Pcr ◽  
Ectopic Expression ◽  
Rank Correlation ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cell Migration And Invasion

Abstract Background Ectopic expression of CDX2 is associated with the development and progression of gastric cancer. Previous studies showed that CDX2 may be an upstream regulator of Reg IV expression in gastric cancer, and our previous report showed that Reg IV upregulated SOX9 expression and enhanced cell migration and invasion in gastric cancer cells. However, the regulatory roles of CDX2 have not been clarified in gastric cancer, and the correlation between CDX2 and Reg IV requires further study. Methods CDX2 and Reg IV were examined in gastric cancer specimens and paired adjacent tissues via real-time PCR and immunohistochemistry (IHC). The association between CDX2 and Reg IV was assessed using the χ2-test and Spearman’s rank correlation. To verify their relationship, knockdown and exogenous expression of CDX2 or Reg IV were performed in AGS and MKN-45 gastric cancer cells, and their expression was subsequently analyzed via a real-time PCR and western blotting. Wound-healing and Transwell assays were used to examine migration and invasion in AGS and MKN-45 cells following CDX2 silencing or overexpression. Results A positive correlation was observed between CDX2 and Reg IV expression at the mRNA and protein levels in gastric cancer tissues. CDX2 silencing significantly downregulated Reg IV expression, and CDX2 overexpression significantly upregulated Reg IV expression in AGS and MKN-45 cells. Neither Reg IV silencing nor overexpression had any effect on CDX2 protein expression in AGS or MKN-45 cells, even though both affected the expression of CDX2 mRNA. Functionally, CDX2 silencing significantly inhibited cell migration and invasion, and CDX2 overexpression significantly promoted cell migration and invasion in AGS and MKN-45 cells. Conclusions Our findings demonstrate that CDX2 expression was positively correlated with that of Reg IV in gastric cancer, and CDX2 promoted cell migration and invasion through upregulation of Reg IV expression in AGS and MKN-45 cells.

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