Smilax glabra Roxb. Inhibits Collagen Induced Adhesion and Migration of PC3 and LNCaP Prostate Cancer Cells through the Inhibition of Beta 1 Integrin Expression

Smilax glabra Roxb. (SGR) has been used as a traditional medicine for brucellosis and syphilis. In this study, we investigated whether nontoxicological levels of water extract of SGR (WESGR) are effective for suppressing steps in the progression of prostate cancer, such as collagen-mediated migration and adhesion and identified the target molecule responsible for such effects. We found that nontoxicological levels of WESGR did not attenuate PC3 and LNCaP cell adhesion to serum but did significantly do so with collagen. In addition, using the Boyden chamber assay, we found that nontoxicological levels of WESGR did not inhibit the migration of PC3 and LNCaP cells to a serum-coated area but did significantly attenuate migration to a collagen-coated area. Interestingly, the expression of α2β1 integrin, a known receptor of collagen, was not affected by ectopic administration of WESGR. However, WESGR significantly attenuated the expression of β1 integrin, but not α2 integrin when PC3 and LNCaP cells were placed on a collagen-coated plate, resulting in attenuation of focal adherent kinase phosphorylation. Finally, 5-O-caffeoylquinic acid was determined as a functional single component which is responsible for antiprostate cancer effects of WESGR. Taken together, our results suggest a novel molecular mechanism for WESGR-mediated antiprostate cancer effects at particular steps such as with migration and adhesion to collagen, and it could provide the possibility of therapeutic use of WESGR against prostate cancer progression.

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Tumor protein D52 (isoform 3) contributes to prostate cancer cell growth via targeting nuclear factor-κB transactivation in LNCaP cells

Tumor Biology ◽

10.1177/1010428317698382 ◽

2017 ◽

Vol 39 (5) ◽

pp. 101042831769838 ◽

Cited By ~ 8

Author(s):

Chandrashekhar Dasari ◽

Dattu Prasad Yaghnam ◽

Reinhard Walther ◽

Ramesh Ummanni

Keyword(s):

Prostate Cancer ◽

Cell Adhesion ◽

Cancer Progression ◽

Underlying Mechanism ◽

Nuclear Factor Κb ◽

Tissue Inhibitor Of Metalloproteinase ◽

Nuclear Factor ◽

Prostate Cancer Progression ◽

Lncap Cells ◽

Cancer Cell Growth

Our previous study showed that TPD52 overexpression could increase migration and proliferation of LNCaP cells contributing to the development of prostate cancer. However, mechanism of TPD52 in prostate cancer initiation and progression remains elusive. In this study, we investigated the possible underlying mechanism of TPD52 in prostate cancer progression. In LNCaP cells, TPD52 expression was altered by transfecting with either EGFP-TPD52 or specific short hairpin RNA. Overexpression of TPD52 protected LNCaP cells from apoptosis through elevated anti-apoptotic proteins XIAP, Bcl-2, and Cyclin D1, whereas Bax was downregulated. Mechanistically, we found that TPD52 confers transactivation of nuclear factor-κB, thereby enhancing its target gene expression in LNCaP cells. TPD52 promotes LNCaP cell invasion probably via increased matrix metalloproteinase 9 expression and its activity while tissue inhibitor of metalloproteinase expression is significantly downregulated. Notably, TPD52 might be involved in cell adhesion, promoting tumor metastasis by inducing loss of E-cadherin, expression of vimentin and vascular cell adhesion molecule, and additionally activation of focal adhesion kinase. Furthermore, TPD52 directly interacts with nuclear factor-κB p65 (RelA) and promotes accumulation of phosphorylated nuclear factor-κB (p65)S536 that is directly linked with nuclear factor-κB transactivation. Indeed, depletion of TPD52 or inhibition of nuclear factor-κB in TPD52-positive cells inhibited secretion of tumor-related cytokines and contributes to the activation of STAT3, nuclear factor-κB, and Akt. Interestingly, in TPD52 overexpressing LNCaP cells, nuclear factor-κB inhibition prevented the autocrine/paracrine activation of STAT3. TPD52 activates STAT3 through ascertaining a cross talk between the nuclear factor-κB and the STAT3 signaling systems. Collectively, these results reveal mechanism by which TPD52 is associated with prostate cancer progression and highlight the approach for therapeutic targeting of TPD52 in prostate cancer.

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Silencing of ELK3 Induces S-M Phase Arrest and Apoptosis and Upregulates SERPINE1 Expression Reducing Migration in Prostate Cancer Cells

BioMed Research International ◽

10.1155/2020/2406159 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Yuanshen Mao ◽

Wenfeng Li ◽

Bao Hua ◽

Xin Gu ◽

Weixin Pan ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Progression ◽

Prostate Cancer Cells ◽

Migration Inhibition ◽

Akt Inhibitor ◽

Phase Arrest ◽

M Phase ◽

And Migration

ELK3, an ETS domain-containing transcription factor, participates in various physiological and pathological processes including cell proliferation, migration, angiogenesis, and malignant progression. However, the role of ELK3 in prostate cancer cells and its mechanism are not fully understood. The contribution of ELK3 to prostate cancer progression was investigated in the present study. We showed that silencing of ELK3 by siRNA in prostate cancer cell DU145 induced S-M phase arrest, promoted apoptosis, inhibited cell proliferation and migration in vitro, and suppressed xenograft growth in mice in vivo. In accordance with its ability to arrest cells in S-M phase, the expression of cyclin A and cyclin B was downregulated. In addition, the expression of p53 was upregulated following ELK3 knockdown, while that of antiapoptotic Bcl-2 was decreased. The migration inhibition may partly due to upregulation of SERPINE1 (a serine protease inhibitor) followed ELK3 knockdown. Consistently, downregulation of SERPINE1 resulted in a modest elimination of migration inhibition resulted from ELK3 knockdown. Furthermore, we found that the AKT signaling was activated in ELK3 knockdown cells, and treatment these cells with AKT inhibitor attenuated SERPINE1 expression induced by ELK3 silencing, suggesting that activation of AKT pathway may be one of the reasons for upregulation of SERPINE1 after ELK3 knockdown. In conclusion, modulation of ELK3 expression may control the progression of prostate cancer partly by regulating cell growth, apoptosis, and migration.

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PAQR6 expression enhancement suggests a worse prognosis in prostate cancer patients

Open Life Sciences ◽

10.1515/biol-2018-0061 ◽

2018 ◽

Vol 13 (1) ◽

pp. 511-517 ◽

Cited By ~ 1

Author(s):

Bin Li ◽

Zhe Lin ◽

Quan Liang ◽

Yuan Hu ◽

Wen-Feng Xu

Keyword(s):

Prostate Cancer ◽

Mrna Expression ◽

Cancer Progression ◽

Survival Rates ◽

Mapk Signaling ◽

Du145 Cell ◽

Kaplan Meier ◽

Prostate Cancer Development ◽

And Migration ◽

Cancer Tissues

AbstractObjectiveThis study aimed to evaluate the expression of progestin and adipoQ receptor family member VI (PAQR6, mPRδ) in prostate cancer and to explore its role in prostate cancer progression.MethodsPAQR6 mRNA expression was evaluated based on the data obtained from the TCGA database and the GEO database. The prognostic value of PAQR6 was explored by Kaplan-Meier analysis. To investigate the role of PAQR6, it was depleted by siRNA in DU145 cells. The effects of depleting PAQR6 on DU145 cell viability and migration were determined by CCK8 assay, colony formation assay, and wound healing assay, respectively. The activation of MEK and ERK were analyzed by western blot.ResultsPAQR6 mRNA expression was significantly up-regulated in prostate cancer tissues and correlated with lower survival rates (p=0.014). Furthermore, qPCR revealed that PAQR6 expression was elevated in DU145 and LNCaP cells compared with RWPE-2 cells. Depleting PAQR6 obviously suppressed DU145 cell proliferation and migration (p<0.01). In addition, the ratio of p-MEK/MEK and p-ERK/ERK was significantly reduced after silencing PAQR6 (p<0.01).ConclusionPAQR6 might play a facilitating role in prostate cancer development by regulating the MAPK signaling pathway. Moreover, it might serve as a potential predictor and therapeutic target in prostate cancer.

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Silencing of MBD1 and MeCP2 in prostate-cancer-derived PC3 cells produces differential gene expression profiles and cellular phenotypes

Bioscience Reports ◽

10.1042/bsr20080032 ◽

2008 ◽

Vol 28 (6) ◽

pp. 319-326 ◽

Cited By ~ 16

Author(s):

Ahmed Yaqinuddin ◽

Farhat Abbas ◽

Syed Z. Naqvi ◽

Mohammad U. Bashir ◽

Romena Qazi ◽

...

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Mrna Expression ◽

Cellular Proliferation ◽

Expression Profiles ◽

Boyden Chamber ◽

Invasion And Migration ◽

Pc3 Cells ◽

And Migration

Alterations in genomic CpG methylation patterns have been found to be associated with cell transformation and neoplasia. Although it is recognized that methylation of CpG residues negatively regulates gene expression, how the various MBPs (methyl-binding proteins) contribute to this process remains elusive. To determine whether the two well characterized proteins MeCP2 (methyl-CpG-binding protein 2) and MBD1 (methyl-CpG-binding domain 1) have distinct or redundant functions, we employed RNAi (RNA interference) to silence their expression in the prostate cancer-derived PC3 cell line, and subsequently compared cell growth, invasion and migration properties of these cell lines in addition to their respective mRNA-expression profiles. Cells devoid of MeCP2 proliferated more poorly compared with MBD1-deficient cells and the parental PC3 cells. Enhanced apoptosis was observed in MeCP2-deficient cells, whereas apoptosis in parental and MBD1-deficient cells appeared to be equivalent. Boyden chamber invasion and wound-healing migration assays showed that MBD1-silenced cells were both more invasive and migratory compared with MeCP2-silenced cells. Finally, gene chip microarray analyses showed striking differences in the mRNA-expression profiles obtained from MeCP2- and MBD1-depleted cells relative to each other as well as when compared with control cells. The results of the present study suggest that MeCP2 and MBD1 silencing appear to affect cellular processes independently in vivo and that discrete sets of genes involved in cellular proliferation, apoptosis, invasion and migration are targeted by each protein.

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Expression and Function of Lysophosphatidic Acid LPA1 Receptor in Prostate Cancer Cells

Endocrinology ◽

10.1210/en.2005-1635 ◽

2006 ◽

Vol 147 (10) ◽

pp. 4883-4892 ◽

Cited By ~ 55

Author(s):

Rishu Guo ◽

Elizabeth A. Kasbohm ◽

Puneeta Arora ◽

Christopher J. Sample ◽

Babak Baban ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Androgen Receptor ◽

Cancer Cells ◽

Lysophosphatidic Acid ◽

Cell Cycle Progression ◽

Receptor Activation ◽

Lncap Cells ◽

Prostate Cancer Cells ◽

And Migration

The bioactive phospholipid lysophosphatidic acid (LPA) promotes cell proliferation, survival, and migration by acting on cognate G protein-coupled receptors named LPA1, LPA2, and LPA3. We profiled gene expression of LPA receptors in androgen-dependent and androgen-insensitive prostate cancer cells and found that LPA1 gene is differentially expressed in androgen-insensitive and LPA-responsive but not androgen-dependent and LPA-resistant cells. In human prostate specimens, expression of LPA1 gene was significantly higher in the cancer compared with the benign tissues. The androgen-dependent LNCaP cells do not express LPA1 and do not proliferate in response to LPA stimulation, implying LPA1 transduces cell growth signals. Accordingly, stable expression of LPA1 in LNCaP cells rendered them responsive to LPA-induced cell proliferation and decreased their doubling time in serum. Implantation of LNCaP-LPA1 cells resulted in increased rate of tumor growth in animals compared with those tumors that developed from the wild-type cells. Growth of LNCaP cells depends on androgen receptor activation, and we show that LPA1 transduces Gαi-dependent signals to promote nuclear localization of androgen receptor and cell proliferation. In addition, treatment with bicalutamide inhibited LPA-induced cell cycle progression and proliferation of LNCaP-LPA1 cells. These results suggest the possible utility of LPA1 as a drug target to interfere with progression of prostate cancer.

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Identification of a novel Protein Disulfide-isomerase A3 (PDIA3) transcript variant as a potential biomarker associated with late stage prostate cancer

10.21203/rs.2.17515/v1 ◽

2019 ◽

Author(s):

Maria Araceli Diaz Cruz ◽

Pontus Karlsson ◽

Gustav Högberg ◽

Sandra Karlsson ◽

Ferenc Szekeres ◽

...

Keyword(s):

Prostate Cancer ◽

Vitamin D ◽

Cancer Progression ◽

Vitamin D Receptor ◽

Digital Pcr ◽

Droplet Digital Pcr ◽

Receptor Protein ◽

Lncap Cells ◽

Transcript Isoforms ◽

Potential Biomarker

Abstract Background Prostate cancer (PC) is a heterogeneous and unpredictable disease and becomes untreatable when the tumor progress to castrate-resistant (CR) or androgen independent (AI). A major clinical challenge in prostate cancer is the lack of diagnostic and prognostic tests that distinguish between benign and aggressive tumors. Isoforms of gene transcripts are emerging as suitable candidates to represent disease progression. Vitamin D receptor (VDR and PDIA3) transcript isoforms could be the target candidates of study since they have been related with anti-tumoral effects and carcinogenesis in several cancer types. Methods The current study investigates the role of vitamin D receptor transcript isoforms in prostate cancer progression by using Next Generation Sequencing (NGS), Droplet Digital PCR (ddPCR) and several functional prediction tools. Results The NGS analysis revealed a novel PDIA3 transcript isoform (PDIA3N) that is higher expressed than the PDIA3 isoform that codifies for the receptor protein, in prostate cells. The expression of PDIA3N was validated by droplet digital PCR (ddPCR) absolute quantification, which confirmed the findings from the NGS analyses. The PDIA3N isoform was present in higher levels than PDIA3, in the metastatic androgen dependent LNCaP cells. Furthermore, analysis of the novel PDIA3 isoform sequence indicate that the variations present in its sequence are altering the original protein function and structure as well as the predicted subcellular localization of the protein. Conclusions We conclude that, PDIA3N due to the high expression in LNCaP cells and its abnormality in predicted structure, localization and function, is a potential biomarker for prostate cancer disease that needs to be further investigated in prostate cancer samples.

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Androgen receptor as a regulator of ZEB2 expression and its implications in epithelial-to-mesenchymal transition in prostate cancer

Endocrine Related Cancer ◽

10.1530/erc-13-0514 ◽

2014 ◽

Vol 21 (3) ◽

pp. 473-486 ◽

Cited By ~ 18

Author(s):

Sheeba Jacob ◽

S Nayak ◽

Gwendolyn Fernandes ◽

R S Barai ◽

S Menon ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Cancer Metastasis ◽

Epithelial To Mesenchymal Transition ◽

Negative Regulator ◽

Lncap Cells ◽

Mesenchymal Transition ◽

Positive Regulator ◽

And Migration ◽

Zeb2 Expression

Zinc finger E-box-binding protein 2 (ZEB2) is known to help mediate the epithelial-to-mesenchymal transition, and thereby it facilitates cancer metastasis. This study was initiated to explore whether ZEB2 expression differs in prostate cancer (PCa,n=7) and benign prostatic hyperplasia (BPH,n=7) tissues. In PCa tissues, the levels of both immunoreactive ZEB2 and androgen receptor (AR) were found to be significantly higher (P<0.05) when compared with BPH tissues. Co-regulation of AR and ZEB2 prompted us to investigate the role of androgenic stimuli in ZEB2 expression. ZEB2 expression was found to be significantly (P<0.05) upregulated after androgen stimulation and downregulated following AR silencing in LNCaP cells, an androgen-dependent PCa cell line. This finding suggested AR as a positive regulator of ZEB2 expression in androgen-dependent cells. Paradoxically, androgen-independent (AI) cell lines PC3 and DU145, known to possess low AR levels, showed significantly (P<0.05) higher expression of ZEB2 compared with LNCaP cells. Furthermore, forced expression of AR in PC3 (PC3-AR) and DU145 (DU-AR) cells led to reductions in ZEB2 expression, invasiveness, and migration. These cells also exhibited an increase in the levels of E-cadherin (a transcriptional target of ZEB2). Co-transfection ofARandZEB2cDNA constructs prevented the decline in invasiveness and migration to a significant extent. Additionally, ZEB2 downregulation was associated with an increase in miR200a/miR200b levels in PC3-AR cells and with a decrease in miR200a/miR200b levels in AR-silenced LNCaP cells. Thus, AR acts as a positive regulator of ZEB2 expression in androgen-dependent cells and as a negative regulator in AI PCa cells.

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CD117/c-kit Defines a Prostate CSC-Like Subpopulation Driving Progression and TKI Resistance

10.1101/256107 ◽

2018 ◽

Cited By ~ 1

Author(s):

Koran S. Harris ◽

Lihong Shi ◽

Brittni M. Foster ◽

Mary E. Mobley ◽

Phyllis L. Elliott ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Cancer Progression ◽

Kinase Inhibitors ◽

Marker Gene ◽

Dependent Manner ◽

Tumor Initiation ◽

Cancer Aggressiveness ◽

Tki Resistance ◽

And Migration

ABSTRACTCancer stem-like cells (CSCs) are associated with cancer progression, metastasis, and recurrence, and may also represent a subset of circulating tumor cells (CTCs). In our prior study, CTCs in advanced prostate cancer patients were found to express CD117/c-kit in a liquid biopsy. Whether CD117 expression played an active or passive role in the aggressiveness and migration of these CTCs remained an open question. In this study, we show that CD117 expression in prostate cancer patients is associated with decreased overall and progression-free survival and that activation and phosphorylation of CD117 increases in prostate cancer patients with higher Gleason grades. To determine how CD117 expression and activation by its ligand stem cell factor (SCF, kit ligand, steel factor) alter prostate cancer aggressiveness, we used LNCaP-C4-2 and PC3-mm human prostate cancer cells, which contain a CD117+ subpopulation. We demonstrate that CD117+ cells display increased proliferation and migration. In prostaspheres, CD117 expression enhances sphere formation. In both 2D and 3D cultures, stemness marker gene expression is higher in CD117+ cells. Using xenograft limiting dilution assays and serial tumor initiation assays, we show that CD117+ cells represent a CSC population. Combined, these data indicate that CD117 expression potentially promotes tumor initiation and metastasis. Further, in cell lines, CD117 activation by SCF promotes faster proliferation and invasiveness, while blocking CD117 activation with tyrosine kinase inhibitors (TKIs) decreased progression in a context-dependent manner. We demonstrate that CD117 expression and activation drives prostate cancer aggressiveness through the CSC phenotype and TKI resistance.

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A Novel Androgen-Induced lncRNA FAM83H-AS1 Promotes Prostate Cancer Progression via the miR-15a/CCNE2 Axis

Frontiers in Oncology ◽

10.3389/fonc.2020.620306 ◽

2021 ◽

Vol 10 ◽

Author(s):

Bo Liu ◽

Duocheng Qian ◽

Weidong Zhou ◽

Huiyang Jiang ◽

Zhendong Xiang ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cancer Progression ◽

Bioinformatics Analysis ◽

Noncoding Rnas ◽

Prostate Adenocarcinoma ◽

Prostate Cancer Progression ◽

Loss Of Function ◽

Bladder Urothelial Carcinoma ◽

And Migration

Prostate cancer (PCa) is one of the most common types of tumors among males worldwide. However, the roles of long noncoding RNAs (lncRNAs) in PCa remain unclear. This study shows that lncRNA FAM83H-AS1 is upregulated in prostate adenocarcinoma, bladder urothelial carcinoma, and kidney renal papillary cell carcinoma samples. Androgen receptor (AR) signaling plays the most important role in PCa tumorigenesis and development. In this study, the results validate that AR signaling is involved in upregulating FAM83H-AS1 expression in PCa cells. Loss-of-function assays demonstrate that FAM83H-AS1 acts as an oncogene in PCa by modulating cell proliferation, cell cycle, and migration. Bioinformatics analysis demonstrates that FAM83H-AS1 is remarkably related to the regulation of the cell cycle and DNA replication through affecting multiple regulators related to these pathways, such as CCNE2. Mechanically, we found that FAM83H-AS1 plays its roles through sponging miR-15a to promote CCNE2 expression. These findings indicate that FAM83H-AS1 is a novel diagnostic and therapeutic marker for PCa.

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Upregulation of SPOCK2 inhibits the invasion and migration of prostate cancer cells by regulating the MT1-MMP/MMP2 pathway

PeerJ ◽

10.7717/peerj.7163 ◽

2019 ◽

Vol 7 ◽

pp. e7163 ◽

Cited By ~ 4

Author(s):

Gang Liu ◽

Fang Ren ◽

Yongsheng Song

Keyword(s):

Prostate Cancer ◽

Matrix Metalloproteinase ◽

Cell Invasion ◽

Mrna Level ◽

Matrix Metalloproteinase 2 ◽

Lncap Cells ◽

Prostate Hyperplasia ◽

Invasion And Migration ◽

Messenger Ribonucleic Acid ◽

And Migration

Background It is known that secreted protein acidic and cysteine rich (osteonectin), cwcv and kazal-like domains proteoglycan 2 (SPOCK2) plays a significant role in the development and progression of several human cancers; however, the role of SPOCK2 in prostate cancer (PCa) remains unclear. This study aimed to find the role and mechanism of SPOCK2 in the development and progression of PCa. Methods The messenger ribonucleic acid (mRNA) expression of SPOCK2 in PCa tissue was detected by real-time polymerase chain reaction (PCR). Upregulation of the SPOCK2 gene was achieved using the DU145 and LNCaP cells by transfecting the cells with SPOCK2 recombinant fragment. Cell invasion and migration ability were detected by transwell chamber and wound healing assay. The expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) and matrix metalloproteinase 2 (MMP2) in the cells was detected by Western Blot and zymography gel assay. Results The mRNA level of SPOCK2 was significantly lower in the PCa tissue compared to benign prostate hyperplasia. Upregulation of SPOCK2 inhibited cell invasion and migration in DU145 and LNCaP cells, inhibited the expression of MT1-MMP and MMP2 and, inhibited activation of MMP2 in DU145 and LNCaP cells. Conclusion SPOCK2 is associated with the progression of PCa. Upregulation of SPOCK2 can inhibit PCa cell invasion and metastasis by decreasing MT1-MMP and MMP2 gene expression and decreasing MMP2 protein activation.

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