scholarly journals TGF-β Effects on Prostate Cancer Cell Migration and Invasion Are Mediated by PGE2 through Activation of PI3K/AKT/mTOR Pathway

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1768-1779 ◽  
Author(s):  
BaoHan T. Vo ◽  
Derrick Morton ◽  
Shravan Komaragiri ◽  
Ana C. Millena ◽  
Chelesie Leath ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Protein Levels ◽  
Prostate Cells ◽  
Pc3 Cells ◽  
Cox 2

Abstract TGF-β plays an important role in the progression of prostate cancer. It exhibits both tumor suppressor and tumor-promoting activities. Correlations between cyclooxygenase (COX)-2 overexpression and enhanced production of prostaglandin (PG)E2 have been implicated in cancer progression; however, there are no studies indicating that TGF-β effects in prostate cancer cells involve PGE2 synthesis. In this study, we investigated TGF-β regulation of COX-1 and COX-2 expression in prostate cancer cells and whether the effects of TGF-β on cell proliferation and migration are mediated by PGE2. COX-1 protein was ubiquitously expressed in prostate cells; however, COX-2 protein levels were detected only in prostate cancer cells. TGF-β treatment increased COX-2 protein levels and PGE2 secretion in PC3 cells. Exogenous PGE2 and PGF2α had no effects on cell proliferation in LNCaP, DU145, and PC3 cells whereas PGE2 and TGF-β induced migration and invasive behavior in PC3 cells. Only EP2 and EP4 receptors were detected at mRNA levels in prostate cells. The EP4-targeting small interfering RNA inhibited PGE2 and TGF-β-induced migration of PC3 cells. TGF-β and PGE2 induce activation of PI3K/AKT/mammalian target of rapamycin pathway as indicated by increased AKT, p70S6K, and S6 phosphorylation. Rapamycin completely blocked the effects of TGF-β and PGE2 on phosphorylation of p70S6K and S6 but not on AKT phosphorylation. PGE2 and TGF-β induced phosphorylation of AKT, which was blocked by antagonists of PGE2 (EP4) receptors (L161982, AH23848) and PI3K inhibitor (LY294002) in PC3 cells. Pretreatment with L161982 or AH23848 blocked the stimulatory effects of PGE2 and TGF-β on cell migration, whereas LY294002 or rapamycin completely eliminated PGE2, TGF-β, and epidermal growth factor-induced migration in PC3 cells. We conclude that TGF-β increases COX-2 levels and PGE2 secretion in prostate cancer cells which, in turn, mediate TGF-β effects on cell migration and invasion through the activation of PI3K/AKT/mammalian target of rapamycin pathway.

scholarly journals Distinct roles for the RNA-binding protein Staufen1 in prostate cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kristen A. Marcellus ◽  
Tara E. Crawford Parks ◽  
Shekoufeh Almasi ◽  
Bernard J. Jasmin
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Rna Binding ◽  
Prostate Cancer Cell ◽  
Rna Binding Protein ◽  
Migration And Invasion ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Prostate Cells

Abstract Background Prostate cancer is one of the most common malignant cancers with the second highest global rate of mortality in men. During the early stages of disease progression, tumour growth is local and androgen-dependent. Despite treatment, a large percentage of patients develop androgen-independent prostate cancer, which often results in metastases, a leading cause of mortality in these patients. Our previous work on the RNA-binding protein Staufen1 demonstrated its novel role in cancer biology, and in particular rhabdomyosarcoma tumorigenesis. To build upon this work, we have focused on the role of Staufen1 in other forms of cancer and describe here the novel and differential roles of Staufen1 in prostate cancer. Methods Using a cell-based approach, three independent prostate cancer cell lines with different characteristics were used to evaluate the expression of Staufen1 in human prostate cancer relative to control prostate cells. The functional impact of Staufen1 on several key oncogenic features of prostate cancer cells including proliferation, apoptosis, migration and invasion were systematically investigated. Results We show that Staufen1 levels are increased in all human prostate cancer cells examined in comparison to normal prostate epithelial cells. Furthermore, Staufen1 differentially regulates growth, migration, and invasion in the various prostate cancer cells assessed. In LNCaP prostate cancer cells, Staufen1 regulates cell proliferation through mTOR activation. Conversely, Staufen1 regulates migration and invasion of the highly invasive, bone metastatic-derived, PC3 prostate cells via the activation of focal adhesion kinase. Conclusions Collectively, these results show that Staufen1 has a direct impact in prostate cancer development and further demonstrate that its functions vary amongst the prostate cancer cell types. Accordingly, Staufen1 represents a novel target for the development of much-needed therapeutic strategies for prostate cancer.

scholarly journals Differential roles and activation of mammalian target of rapamycin complexes 1 and 2 during cell migration in prostate cancer cells

The Prostate ◽  
2020 ◽  
Vol 80 (5) ◽  
pp. 412-423 ◽  
Author(s):  
Smrruthi Vaidegi Venugopal ◽  
Silvia Caggia ◽  
DaJhnae Gambrell‐Sanders ◽  
Shafiq A. Khan
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Prostate Cancer Cells

scholarly journals SFMBT2 (Scm-like with four mbt domains 2) negatively regulates cell migration and invasion in prostate cancer cells

Oncotarget ◽  
2016 ◽  
Vol 7 (30) ◽  
pp. 48250-48264 ◽  
Author(s):  
Jungsug Gwak ◽  
Jee Yoon Shin ◽  
Kwanghyun Lee ◽  
Soon Ki Hong ◽  
Sangtaek Oh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Cell Migration And Invasion

scholarly journals Identification of PIM1 substrates reveals a role for NDRG1 in prostate cancer cellular migration and invasion

2020 ◽  
Author(s):  
Russell J. Ledet ◽  
Sophie Ruff ◽  
Yu Wang ◽  
Shruti Nayak ◽  
Jeffrey A. Schneider ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Genetic Screen ◽  
Cellular Migration ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Cell Migration And Invasion ◽  
Chemical Genetic

ABSTRACTPIM1 is an oncogenic serine/threonine kinase that promotes and maintains prostate tumorigenesis. To more fully understand the mechanism by which PIM1 promotes oncogenesis, we performed a chemical genetic screen to identify direct PIM1 substrates in prostate cancer cells. The PIM1 substrates we identified were involved in a variety of oncogenic processes, and included N-Myc Downstream-Regulated Gene 1 (NDRG1), which has reported roles in the suppression of cancer cell invasion and metastasis. NDRG1 is phosphorylated by PIM1 at serine 330 (pS330), and the level of NDRG1 pS330 is associated with high grade compared to low grade prostate tumors. While NDRG1 pS330 is largely cytoplasmic, total NDRG1 is both cytoplasmic and nuclear. Mechanistically, PIM1 phosphorylation of NDRG1 decreases its stability, reducing its interaction with AR, and thereby lowering expression of AR target genes. PIM1-dependent NDRG1 phosphorylation also reduces NDRG1’s ability to suppress prostate cancer cell migration and invasion. Our study identifies a novel set of PIM1 substrates in prostate cancer cells using a direct, unbiased chemical genetic screen. It also provides key insights into the mechanisms by which PIM1-mediated phosphorylation of NDRG1 impairs its function, resulting in enhanced cell migration and invasion.

scholarly journals Effects of the Bone/Bone Marrow Microenvironments on Prostate Cancer Cells and CD59 Expression

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Bo Yan ◽  
Yan Li ◽  
Shaoju Min ◽  
Peng Zhang ◽  
Bin Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Bone Marrow ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Cell Cycle Distribution ◽  
Prostate Cancer Cells ◽  
Pc3 Cells ◽  
Bone Marrow Microenvironments

Objective. To evaluate the effects of human bone marrow mesenchymal stem cells (hBMSCs) and osteoblasts (hFOB1.19) on PC3 prostate cancer cells. Methods. To simulate the in vivo interaction between the bone/bone marrow microenvironments and prostate cancer cells, we established cocultures of PC3 cells with hBMSC or hFOB1.19 cells and evaluated their effects on the proliferation, cell cycle distribution, cell migration, and invasion of PC3 cells. Quantitative reverse transcription polymerase chain reaction was used to detect CD59 mRNA expression in PC3 cells. The expression of receptor activator of nuclear factor- (NF-) κB (RANK), RANK ligand (RANKL), osteoprotegerin (OPG), CD59, NF-κB (p50 subunit), and cyclin D1 in PC3 cells was analyzed by immunofluorescence and western blotting. Results. hBMSCs and hFOB1.19 cells enhanced the proliferation, migration, and invasion of PC3 cells; increased the proportion of PC3 cells in the S and G2/M phases of the cell cycle; and upregulated RANK, RANKL, OPG, CD59, cyclin D1, and NF-κB (p50 subunit) expression by PC3 cells. The RANKL inhibitor, scutellarin, inhibited these effects in PC3-hFOB1.19 cocultures. Conclusion. hBMSCs and hFOB1.19 cells modulate the phenotype of PC3 prostate cancer cells and the expression of CD59 by activating the RANK/RANKL/OPG signaling pathway.

scholarly journals Suppression of TRPM7 Inhibited Hypoxia-Induced Migration and Invasion of Androgen-Independent Prostate Cancer Cells by Enhancing RACK1-Mediated Degradation of HIF-1α

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Fei Yang ◽  
Jiarong Cai ◽  
Hailun Zhan ◽  
Jie Situ ◽  
Wenbiao Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Annexin A1 ◽  
Prostate Cancer Cells ◽  
Cell Migration And Invasion ◽  
Androgen Independent

Transient receptor potential melastatin subfamily member 7 (TRPM7) was essential in the growth and metastatic ability of prostate cancer cells. However, the effects and the relevant molecular mechanisms of TRPM7 on metastasis of prostate cancer under hypoxic atmosphere remain unclear. This study investigated the role of TRPM7 in the metastatic ability of androgen-independent prostate cancer cells under hypoxia. First, data mining was carried out to disclose the relationship between the TRPM7 gene level and the survival of prostate cancer patients. Specific siRNAs were used to knockdown target genes. Western blotting and qPCR were employed to determine protein and gene expression, respectively. The gene transcription activity was evaluated by luciferase activity assay of promoter gene. The protein interaction was determined by coimmunoprecipitation. Wound healing and transwell assays were employed to evaluated cell migration and invasion, respectively. Open access database results showed that high expression of TRPM7 was closely related to the poor survival of prostate cancer patients. Hypoxia simultaneously increased TRPM7 expression and induced HIF-1α accumulation in androgen-independent prostate cancer cells. Knockdown of TRPM7 significantly promoted HIF-1α degradation through the proteasome and inhibited EMT changes in androgen-independent prostate cancer cells under hypoxic condition. Moreover, TRPM7 knockdown increased the phosphorylation of RACK1 and strengthened the interaction between RACK1 and HIF-1α but attenuated the binding of HSP90 to HIF-1α. Whereas knockdown of RACK1 increased the binding of HSP90 to HIF-1α. Furthermore, both TRPM7 and HIF-1α knockdown significantly suppressed hypoxia-induced Annexin A1 protein expression, and suppression of HIF-1α/Annexin A1 signaling significantly inhibited hypoxia-induced cell migration and invasion of androgen-independent prostate cancer cells. Our findings demonstrate that TRPM7 knockdown promotes HIF-1α degradation via an oxygen-independent mechanism involving increased binding of RAKC1 to HIF-1α, and TRPM7-HIF-1α-Annexin A1 signaling axis plays a crucial role in the EMT, cell migration, and invasion of androgen-independent prostate cancer cells under hypoxic conditions.

scholarly journals Niclosamide suppresses cell migration and invasion in enzalutamide resistant prostate cancer cells via Stat3-AR axis inhibition

The Prostate ◽  
2015 ◽  
Vol 75 (13) ◽  
pp. 1341-1353 ◽  
Author(s):  
Chengfei Liu ◽  
Wei Lou ◽  
Cameron Armstrong ◽  
Yezi Zhu ◽  
Christopher P Evans ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Prostate Cancer Cells ◽  
Cell Migration And Invasion

scholarly journals AICAR Induces Apoptosis and Inhibits Migration and Invasion in Prostate Cancer Cells Through an AMPK/mTOR-Dependent Pathway

2019 ◽  
Vol 20 (7) ◽  
pp. 1647 ◽  
Author(s):  
Chia-Cheng Su ◽  
Kun-Lin Hsieh ◽  
Po-Len Liu ◽  
Hsin-Chih Yeh ◽  
Shu-Pin Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Cell Growth ◽  
Western Blot ◽  
Cancer Cells ◽  
Mtt Assay ◽  
Migration And Invasion ◽  
Related Protein ◽  
Prostate Cancer Cells ◽  
Dependent Pathway

Current clinical challenges of prostate cancer management are to restrict tumor growth and prohibit metastasis. AICAR (5-aminoimidazole-4-carbox-amide-1-β-d-ribofuranoside), an AMP-activated protein kinase (AMPK) agonist, has demonstrated antitumor activities for several types of cancers. However, the activity of AICAR on the cell growth and metastasis of prostate cancer has not been extensively studied. Herein we examine the effects of AICAR on the cell growth and metastasis of prostate cancer cells. Cell growth was performed by MTT assay and soft agar assay; cell apoptosis was examined by Annexin V/propidium iodide (PI) staining and poly ADP ribose polymerase (PARP) cleavage western blot, while cell migration and invasion were evaluated by wound-healing assay and transwell assay respectively. Epithelial–mesenchymal transition (EMT)-related protein expression and AMPK/mTOR-dependent signaling axis were analyzed by western blot. In addition, we also tested the effect of AICAR on the chemosensitivity to docetaxel using MTT assay. Our results indicated that AICAR inhibits cell growth in prostate cancer cells, but not in non-cancerous prostate cells. In addition, our results demonstrated that AICAR induces apoptosis, attenuates transforming growth factor (TGF)-β-induced cell migration, invasion and EMT-related protein expression, and enhances the chemosensitivity to docetaxel in prostate cancer cells through regulating the AMPK/mTOR-dependent pathway. These findings support AICAR as a potential therapeutic agent for the treatment of prostate cancer.

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