scholarly journals Regulation of eIF4F complex by the peptidyl prolyl isomerase FKBP7 in taxane-resistant prostate cancer

2016 ◽  
Author(s):  
Marine F. Garrido ◽  
Nicolas J-P. Martin ◽  
Catherine Gaudin ◽  
Frédéric Commo ◽  
Nader AL Nakouzi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gene Expression Signature ◽  
Mass Spectrometry Analysis ◽  
Functional Screening ◽  
Protein Homeostasis ◽  
Prolyl Isomerase ◽  
Peptidyl Prolyl Isomerase ◽  
Spectrometry Analysis ◽  
Prostate Cancers ◽  
Chemoresistant Cell

ABSTRACTTargeted therapies that exploit the signaling pathways involved in prostate cancer are required to overcome chemoresistance and improve treatment outcomes for men. Molecular chaperones play a key role in the regulation of protein homeostasis and are potential targets to alleviate chemoresistance. Using image-based high content siRNA functional screening based on a gene expression signature, we identified FKBP7, a molecular chaperone overexpressed in docetaxel-resistant and in cabazitaxel-resistant prostate cancer cells. FKBP7 was upregulated in human prostate cancers and correlated with the recurrence in patients receiving Docetaxel.FKBP7silencing showed that FKBP7 is required to maintain the growth of chemoresistant cell lines and of chemoresistant tumors in mice. Mass spectrometry analysis revealed that FKBP7 interacts with the eIF4G component of the eIF4F translation initiation complex to mediate survival of chemoresistant cells. Using small molecule inhibitors of eIF4A, the RNA helicase component of eIF4F, we were able to overcome docetaxel and cabazitaxel resistance.

scholarly journals Mass Spectrometry Analysis of the Native Protein Complex Containing Actinin-4 in Prostate Cancer Cells

2006 ◽  
Vol 6 (3) ◽  
pp. 479-491 ◽  
Author(s):  
Tomohiko Hara ◽  
Kazufumi Honda ◽  
Miki Shitashige ◽  
Masaya Ono ◽  
Hideyasu Matsuyama ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mass Spectrometry ◽  
Cancer Cells ◽  
Protein Complex ◽  
Mass Spectrometry Analysis ◽  
Native Protein ◽  
Prostate Cancer Cells ◽  
Spectrometry Analysis

scholarly journals Regulation of eIF4F Translation Initiation Complex by the Peptidyl Prolyl Isomerase FKBP7 in Taxane-resistant Prostate Cancer

2018 ◽  
Vol 25 (2) ◽  
pp. 710-723 ◽  
Author(s):  
Marine F. Garrido ◽  
Nicolas J.-P. Martin ◽  
Matthieu Bertrand ◽  
Catherine Gaudin ◽  
Frédéric Commo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Translation Initiation ◽  
Prolyl Isomerase ◽  
Initiation Complex ◽  
Peptidyl Prolyl Isomerase

scholarly journals Bone secreted factors induce cellular quiescence in prostate cancer cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Li-Yuan Yu-Lee ◽  
Yu-Chen Lee ◽  
Jing Pan ◽  
Song-Chang Lin ◽  
Tianhong Pan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Disseminated Tumor Cells ◽  
Dominant Negative ◽  
Mass Spectrometry Analysis ◽  
Pcr Analysis ◽  
Spectrometry Analysis ◽  
Secreted Factors ◽  
Cellular Quiescence ◽  
Inducing Factors

AbstractDisseminated tumor cells (DTCs) undergo a dormant state in the distant metastatic site(s) before becoming overt metastatic diseases. In prostate cancer (PCa), bone metastasis can occur years after prostatectomy, suggesting that bone may provide dormancy-inducing factors. To search for these factors, we prepared conditioned media (CM) from calvariae. Using live-cell imaging, we found that Calvarial-CM treatment increased cellular quiescence in C4-2B4 PCa cells. Mass spectrometry analysis of Calvarial-CM identified 132 secreted factors. Western blot and ELISA analyses confirmed the presence of several factors, including DKK3, BMP1, neogenin and vasorin in the Calvarial-CM. qRT-PCR analysis of total calvariae versus isolated osteoblasts showed that DKK3, BMP1, vasorin and neogenin are mainly expressed by osteoblasts, while MIA, LECT1, NGAL and PEDF are expressed by other calvarial cells. Recombinant human DKK3, BMP1, vasorin, neogenin, MIA and NGAL treatment increased cellular quiescence in both C4-2b and C4-2B4 PCa cells. Mechanistically, DKK3, vasorin and neogenin, but not BMP1, increased dormancy through activating the p38MAPK signaling pathway. Consistently, DKK3, vasorin and neogenin failed to induce dormancy in cells expressing dominant-negative p38αMAPK while BMP1 remained active, suggesting that BMP1 uses an alternative dormancy signaling pathway. Thus, bone secretes multiple dormancy-inducing factors that employ distinct signaling pathways to induce DTC dormancy in bone.

scholarly journals Proteomic analyses Identify Major Vault Protein as a Prognostic Biomarker for Fatal Prostate Cancer

2021 ◽  
Author(s):  
Håkon Ramberg ◽  
Elin Richardsen ◽  
Gustavo A de Souza ◽  
Mehrdad Rakaee ◽  
Maria Ekman Stensland ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Biomarker ◽  
Mass Spectrometry Analysis ◽  
Major Vault Protein ◽  
Net Benefit ◽  
Demographic Shift ◽  
Spectrometry Analysis ◽  
Protein Levels ◽  
Post Surgery ◽  
Risk Parameters

Abstract The demographic shift towards an older population will increase the number of prostate cancer cases. A challenge in the treatment of prostate cancer is to avoid undertreatment of patients at high risk of progression following curative treatment. These men can benefit from early salvage treatment. An explorative cohort consisting of tissue from 16 patients who underwent radical prostatectomy, and were either alive or had died from prostate cancer within 10 years post-surgery, was analyzed by mass spectrometry analysis. Following proteomic and bioinformatic analyses, major vault protein was identified as a putative prognostic biomarker. A publicly available tissue proteomics dataset and a retrospective cohort of 368 prostate cancer patients were used for validation. The prognostic value of the major vault protein was verified by scoring immunohistochemical staining of a tissue microarray. High level of major vault protein was associated with more than four-fold higher risk for death from prostate cancer (HR=4.41, 95% CI: 1.45-13.38; p = 0.009) in a Cox proportional hazard models, adjusted for Cancer of the Prostate Risk Assessments Post-surgical (CAPRA-S) score and perineural invasion. Decision curve analyses suggested an improved standardized net benefit, ranging from 0.06-0.18, of adding major vault protein onto CAPRA-S score. This observation was confirmed by receiver operator characteristics curve analyses for the CAPRA-S score versus CAPRA-S and major vault protein score (AUC: 0.58 vs. 0.73). From these analyses one can infer that major vault protein levels in combination with CAPRA-S score might add onto established risk parameters to identify patients with lethal prostate cancer.

scholarly journals A re-evaluation of LINE-1 ORF2 expression in LNCaP prostate cancer cells

Mobile DNA ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Erica M. Briggs ◽  
Corrado Spadafora ◽  
Susan K. Logan
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cellular Localization ◽  
Mass Spectrometry Analysis ◽  
Hek293 Cells ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Spectrometry Analysis ◽  
Sirna Knockdown ◽  
Long Interspersed Element

Abstract Background We previously examined expression of Long Interspersed Element-1 (LINE-1) in a variety of prostate cancer cells including hormone-dependent LNCaP cells. These studies demonstrated expression and sub-cellular localization of LINE-1 proteins, ORF1p, with antibody 4H1, and ORF2p, with antibody chA1-L1. Results Here we conduct immunoprecipitation/mass spectrometry analysis using chA1-L1 antibody against ORF2p in LNCaP cells. Our results indicate that antigens detected by the antibody include the transcriptional regulator BCLAF1. We show that chA1-L1 recognizes BCLAF1 using siRNA knockdown and overexpression of a tagged BCLAF1. We also show that chA1-L1 antibody recognizes ORF2p in HEK293 cells overexpressing LINE-1. Further, analysis of ORF2p (chA1-L1) and BCLAF1 foci using immunofluorescence in LNCaP cells showed significant colocalization. Conclusions Overall, our findings indicate that chA1-L1 antibody recognizes both BCLAF1 and ORF2p but the majority of antigen recognized in LNCaP cells is BCLAF1.

scholarly journals Purification and Characterization of Cyclophilin-a Proteins That Associated With Protein Folding in Salmonella Typhimurium

2021 ◽  
Author(s):  
Manoj Kumawat ◽  
Irungbam Karuna ◽  
Divya Chaudhary ◽  
Neeraj Ahlawat ◽  
Bilkees Nabi ◽  
...  
Keyword(s):  
Protein Folding ◽  
Sequence Similarity ◽  
Cyclophilin A ◽  
Vital Role ◽  
Host Cells ◽  
Mass Spectrometry Analysis ◽  
Peptidyl Prolyl Isomerase ◽  
Bacterial Physiology ◽  
Spectrometry Analysis

Abstract Salmonella Typhimurium (ST) is the zoonotic pathogenic Gram-negative bacteria to causes infectious disease in humans as well as in animals. It causes gastrointestinal illness and fever called salmonellosis, which is foodborne diarrheal and leading cause of millions of deaths worldwide. Salmonella enterica serovar Typhimurium (S. Typhimurium) during its pathogenesis takeaway the actin cytoskeleton of their host cells and this is the crucial step of its infection cycle. Cyclophilin A, a type of peptidyl-prolyl isomerase that’s encoded by the ppiA gene in ST, plays pleiotropic roles in maintaining bacterial physiology. In this research, the proteomic characterization of the peptidyl-prolyl cis-trans isomerase- A (Cyclophilin A) from Salmonella Typhimurium is reported. Cyclophilin A (CypA) protein from Salmonella Typhimurium proved to be a highly conserved protein sequence and highly homologous compared to other organisms. This protein was expressed in Escherichia coli and then purified in a recombinant form protein exhibited a characteristic PPIases activity (Vmax = 0.8752 ± 0.13892 µmoles/ min, Km = 0.9315 ± 0.5670 µM) in comparison to control. Also, in this study the mass spectrometry analysis of Cyp A protein-peptide showed the highest sequence similarity with the cyclophilin protein of Salmonella. PPIases proteins enzyme data suggest that Ppi-A has roles in the protein folding that may be contributing to the virulence of Salmonella by isomerization of protein outline. These results suggest an active and vital role of this protein in protein folding along with regulation in Salmonella Typhimurium.

scholarly journals Database-augmented Mass Spectrometry Analysis of Exosomes Identifies Claudin 3 as a Putative Prostate Cancer Biomarker

2017 ◽  
Vol 16 (6) ◽  
pp. 998-1008 ◽  
Author(s):  
Thomas Stefan Worst ◽  
Jost von Hardenberg ◽  
Julia Christina Gross ◽  
Philipp Erben ◽  
Martina Schnölzer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mass Spectrometry ◽  
Cancer Biomarker ◽  
Mass Spectrometry Analysis ◽  
Spectrometry Analysis
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