8 results on '"Bourboulia, Dimitra"'
Search Results
2. Editorial: A new chapter for Cell Stress and Chaperones.
- Author
-
Bourboulia D, Blair LJ, Clark MS, Edkins AL, Hightower LE, Mollapour M, Prahlad V, Repasky EA, Truebano M, Truman AW, Truttmann MC, van Oosten-Hawle P, and Woodford MR
- Subjects
- Molecular Chaperones metabolism, Oxidative Stress
- Published
- 2024
- Full Text
- View/download PDF
3. Second Virtual International Symposium on Cellular and Organismal Stress Responses, September 8-9, 2022.
- Author
-
van Oosten-Hawle P, Backe SJ, Ben-Zvi A, Bourboulia D, Brancaccio M, Brodsky J, Clark M, Colombo G, Cox MB, De Los Rios P, Echtenkamp F, Edkins A, Freeman B, Goloubinoff P, Houry W, Johnson J, LaPointe P, Li W, Mezger V, Neckers L, Nillegoda NB, Prahlad V, Reitzel A, Scherz-Shouval R, Sistonen L, Tsai FTF, Woodford MR, Mollapour M, and Truman AW
- Subjects
- Humans, HSP70 Heat-Shock Proteins, Molecular Chaperones physiology, Stress, Physiological physiology
- Abstract
The Second International Symposium on Cellular and Organismal Stress Responses took place virtually on September 8-9, 2022. This meeting was supported by the Cell Stress Society International (CSSI) and organized by Patricija Van Oosten-Hawle and Andrew Truman (University of North Carolina at Charlotte, USA) and Mehdi Mollapour (SUNY Upstate Medical University, USA). The goal of this symposium was to continue the theme from the initial meeting in 2020 by providing a platform for established researchers, new investigators, postdoctoral fellows, and students to present and exchange ideas on various topics on cellular stress and chaperones. We will summarize the highlights of the meeting here and recognize those that received recognition from the CSSI., (© 2022. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
4. Hsp90 chaperone code and the tumor suppressor VHL cooperatively regulate the mitotic checkpoint.
- Author
-
Woodford MR, Backe SJ, Wengert LA, Dunn DM, Bourboulia D, and Mollapour M
- Subjects
- Humans, M Phase Cell Cycle Checkpoints genetics, Mitosis genetics, Molecular Chaperones genetics, Phosphorylation, Protein Binding, Proteolysis, Signal Transduction genetics, Cell Cycle Proteins genetics, Chaperonins genetics, HSP90 Heat-Shock Proteins genetics, Protein Serine-Threonine Kinases genetics, Protein-Tyrosine Kinases genetics, Von Hippel-Lindau Tumor Suppressor Protein genetics
- Abstract
Heat shock protein-90 (Hsp90) is an essential molecular chaperone in eukaryotes that plays a vital role in protecting and maintaining the functional integrity of deregulated signaling proteins in tumors. We have previously reported that the stability and activity of the mitotic checkpoint kinase Mps1 depend on Hsp90. In turn, Mps1-mediated phosphorylation Hsp90 regulates its chaperone function and is essential for the mitotic arrest. Cdc14-assisted dephosphorylation of Hsp90 is vital for the mitotic exit. Post-translational regulation of Hsp90 function is also known as the Hsp90 "Chaperone Code." Here, we demonstrate that only the active Mps1 is ubiquitinated on K86, K827, and K848 by the tumor suppressor von Hippel-Lindau (VHL) containing E3 enzyme, in a prolyl hydroxylation-independent manner and degraded in the proteasome. Furthermore, we show that this process regulates cell exit from the mitotic checkpoint. Collectively, our data demonstrates an interplay between the Hsp90 chaperone and VHL degradation machinery in regulating mitosis., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
5. MMPs, tyrosine kinase signaling and extracellular matrix proteolysis in kidney cancer.
- Author
-
Hashmi F, Mollapour M, Bratslavsky G, and Bourboulia D
- Subjects
- Humans, Signal Transduction, Carcinoma, Renal Cell metabolism, Carcinoma, Renal Cell pathology, Extracellular Matrix metabolism, Kidney Neoplasms metabolism, Kidney Neoplasms pathology, Matrix Metalloproteinases metabolism, Protein-Tyrosine Kinases metabolism, Proteolysis
- Abstract
Patients diagnosed with metastatic renal cell carcinoma (RCC) have ∼12% chance for 5-year survival. The integrity of the extracellular matrix (ECM) that surrounds tumor cells influences their behavior and, when disturbed, it could facilitate local invasion and spread of tumor cells to distant sites. The interplay between von Hippel-Lindau/hypoxia inducible factor signaling axis and activated kinase networks results in aberrant ECM and tumor progression. Matrix metalloproteinases (MMPs) are proteolytic enzymes implicated in ECM remodeling, tumor angiogenesis, and immune cell infiltration. Understanding the cross-talk between kinase signaling and ECM proteolysis in RCC could provide insights into developing drugs that interfere specifically with the process of invasion. In this review, we discuss changes in the MMPs/ECM axis in RCC, prominent kinase signaling pathways implicated in MMPs induction, and comment on emerging extracellular regulatory networks that modulate MMPs activity., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
6. Comprehensive genomic profiling of metastatic collecting duct carcinoma, renal medullary carcinoma, and clear cell renal cell carcinoma.
- Author
-
Bratslavsky G, Gleicher S, Jacob JM, Sanford TH, Shapiro O, Bourboulia D, Gay LM, Andrea Elvin J, Vergilio JA, Suh J, Ramkissoon S, Severson EA, Killian JK, Schrock AB, Chung JH, Miller VA, Mollapour M, and Ross JS
- Subjects
- Adult, Carcinoma, Medullary secondary, Carcinoma, Renal Cell secondary, Female, Genomics, Humans, Kidney Neoplasms pathology, Male, Middle Aged, Mutation, Carcinoma, Medullary genetics, Carcinoma, Renal Cell genetics, Gene Expression Profiling, Kidney Neoplasms genetics
- Abstract
Introduction and Objective: Unlike clear cell renal cell carcinoma (CCRCC), collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) are rare tumors that progress rapidly and appear resistant to current systemic therapies. We queried comprehensive genomic profiling to uncover opportunities for targeted therapy and immunotherapy., Material and Methods: DNA was extracted from 40 microns of formalin-fixed, paraffin-embedded specimen from relapsed, mCDC (n = 46), mRMC (n = 24), and refractory and metastatic (m) mCCRCC (n = 626). Comprehensive genomic profiling was performed, and Tumor mutational burden (TMB) and microsatellite instability (MSI) were calculated. We analyzed all classes of genomic alterations., Results: mCDC had 1.7 versus 2.7 genomic alterations/tumor in mCCRCC ( = 0.04). Mutations in VHL (P < 0.0001) and TSC1 (P = 0.04) were more frequent in mCCRCC. SMARCB1 (P < 0.0001), NF2 (P = 0.0007), RB1 (P = 0.02) and RET (P = 0.0003) alterations were more frequent in mCDC versus mCCRCC. No VHL alterations in mRMC and mCDC were identified. SMARCB1 genomic alterations were significantly more frequent in mRMC than mCDC (P = 0.0002), but were the most common alterations in both subtypes. Mutations to EGFR, RET, NF2, and TSC2 were more frequently identified in mCDC versus mRMC. The median TMB and MSI-High status was low with <1% of mCCRC, mCDC, and mRMC having ≥ 20 mut/Mb., Conclusion: Genomic alteration patterns in mCDC and mRMC differ significantly from mCCRCC. Targeted therapies for mCDC and mRMC appear limited with rare opportunities to target alterations in receptor tyrosine kinase and MTOR pathways. Similarly, TMB and absence of MSI-High status in mCDC and mRMC suggest resistance to immunotherapies., (Copyright © 2020. Published by Elsevier Inc.)
- Published
- 2021
- Full Text
- View/download PDF
7. The Role of Heat Shock Protein-90 in the Pathogenesis of Birt-Hogg-Dubé and Tuberous Sclerosis Complex Syndromes.
- Author
-
Woodford MR, Backe SJ, Sager RA, Bourboulia D, Bratslavsky G, and Mollapour M
- Subjects
- Angiomyolipoma etiology, Carcinoma, Renal Cell etiology, Humans, Kidney Neoplasms etiology, Birt-Hogg-Dube Syndrome etiology, HSP90 Heat-Shock Proteins physiology, Tuberous Sclerosis etiology
- Abstract
Birt-Hogg-Dubé (BHD) and tuberous sclerosis (TS) syndromes share many clinical features. These two diseases display distinct histologic subtypes of renal tumors: chromophobe renal cell carcinoma and renal angiomyolipoma, respectively. Early work suggested a role for mTOR dysregulation in the pathogenesis of these two diseases, however their detailed molecular link remains elusive. Interestingly, a growing number of case reports describe renal angiomyolipoma in BHD patients, suggesting a common molecular origin. The BHD-associated proteins FNIP1/2 and the TS protein Tsc1 were recently identified as regulators of the molecular chaperone Hsp90. Dysregulation of Hsp90 activity has previously been reported to support tumorigenesis, providing a potential explanation for the overlapping phenotypic manifestations in these two hereditary syndromes., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
8. Endogenous angiogenesis inhibitor blocks tumor growth via direct and indirect effects on tumor microenvironment.
- Author
-
Bourboulia D, Jensen-Taubman S, Rittler MR, Han HY, Chatterjee T, Wei B, and Stetler-Stevenson WG
- Subjects
- Adenocarcinoma enzymology, Animals, Apoptosis physiology, Cell Movement, Cell Proliferation, Female, Focal Adhesion Protein-Tyrosine Kinases metabolism, Humans, Lung Neoplasms enzymology, Mice, Mice, Nude, Microvessels, Neoplasm Invasiveness, Neoplasm Transplantation, Proto-Oncogene Proteins c-akt metabolism, Tissue Inhibitor of Metalloproteinase-2 metabolism, Transplantation, Heterologous, Tumor Cells, Cultured, Adenocarcinoma blood supply, Lung Neoplasms blood supply, Matrix Metalloproteinase Inhibitors, Neovascularization, Pathologic enzymology, Tissue Inhibitor of Metalloproteinase-2 physiology, Tumor Microenvironment physiology
- Abstract
Tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) belongs to a small family of endogenous proteins that inhibits a group of enzymes, the matrix metalloproteinases (MMPs). TIMP-2 inhibits endothelial cell proliferation and migration in vitro and angiogenesis in vivo, through MMP-dependent and -independent mechanisms. However, little is known regarding the contribution of these mechanisms to the antitumor effects of TIMP-2. Using a retroviral delivery system, we stably overexpressed TIMP-2 and its mutant Ala+TIMP-2 (devoid of MMP inhibitory activity) in human adenocarcinoma A549 cells. Using real time PCR, and enzyme-linked immunosorbent assay (ELISA), we confirmed enhanced TIMP-2 expression and its MMP inhibitory activity by reverse zymography. In vitro, growth assays suggested that TIMP-2 and Ala+TIMP-2 did not alter basal cell proliferation rates, however, tumor cell migration and invasion were inhibited. In vivo, both TIMP-2 and Ala+TIMP-2 A549 xenografts exhibited reduced growth rate, CD31 immunostaining indicated decreased intratumoral microvascular density, and TUNEL demonstrated enhanced tumor cell apoptosis. Immunoblotting and immunohistochemical analyses of A549 xenograft tissues with either phospho-FAK (Tyr397) or phospho-AKT (Ser473) showed decreased activation in both TIMP-2 and Ala+TIMP-2 tumor cells. We conclude that TIMP-2-mediated inhibition of tumor growth occurs, at least in part, independently of MMP inhibition, and is a consequence of both direct effects of TIMP-2 on tumor cells and modulation of the tumor microenvironment., (Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.