2021
Mickova, Alena; Kharaishvili, Gvantsa; Kurfurstova, Daniela; Gachechiladze, Mariam; Kral, Milan; Vacek, Ondrej; Pokryvkova, Barbora; Mistrik, Martin; Soucek, Karel; Bouchal, Jan
Skp2 and Slug Are Coexpressed in Aggressive Prostate Cancer and Inhibited by Neddylation Blockade. Journal Article
In: International journal of molecular sciences, vol. 22, no. 6, 2021, ISSN: 1422-0067, (Place: Switzerland).
Abstract | Links | BibTeX | Tags: *Protein Processing, Androgen/genetics/metabolism, Antigens, Antineoplastic Agents/pharmacology, Cadherins/genetics/metabolism, CD/genetics/metabolism, Cell Line, Cell Survival/drug effects, Cyclin-Dependent Kinase Inhibitor p27/genetics/metabolism, Cyclopentanes/pharmacology, Docetaxel/pharmacology, Epithelial-Mesenchymal Transition/genetics, Gene Expression Regulation, Humans, Immunohistochemistry, Lymphatic Metastasis, Male, multiplex, NEDD8 Protein/*genetics/metabolism, neddylation, Neoplasm Grading, Neoplastic, PC-3 Cells, Post-Translational, Prostate cancer, Prostate/metabolism/pathology, Prostatic Neoplasms/*genetics/metabolism/pathology, Pyrimidines/pharmacology, Receptors, RNA, S-Phase Kinase-Associated Proteins/antagonists & inhibitors/*genetics/metabolism, Skp2 (S-phase kinase-associated protein 2), Slug, Small Interfering/genetics/metabolism, Snail Family Transcription Factors/*genetics/metabolism, Tumor
@article{mickova_skp2_2021,
title = {Skp2 and Slug Are Coexpressed in Aggressive Prostate Cancer and Inhibited by Neddylation Blockade.},
author = {Alena Mickova and Gvantsa Kharaishvili and Daniela Kurfurstova and Mariam Gachechiladze and Milan Kral and Ondrej Vacek and Barbora Pokryvkova and Martin Mistrik and Karel Soucek and Jan Bouchal},
doi = {10.3390/ijms22062844},
issn = {1422-0067},
year = {2021},
date = {2021-03-01},
journal = {International journal of molecular sciences},
volume = {22},
number = {6},
abstract = {Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men in Western countries, and there is still an urgent need for a better understanding of PCa progression to inspire new treatment strategies. Skp2 is a substrate-recruiting component of the E3 ubiquitin ligase complex, whose activity is regulated through neddylation. Slug is a transcriptional repressor involved in the epithelial-to-mesenchymal transition, which may contribute to therapy resistance. Although Skp2 has previously been associated with a mesenchymal phenotype and prostate cancer progression, the relationship with Slug deserves further elucidation. We have previously shown that a high Gleason score (≥8) is associated with higher Skp2 and lower E-cadherin expression. In this study, significantly increased expression of Skp2, AR, and Slug, along with E-cadherin downregulation, was observed in primary prostate cancer in patients who already had lymph node metastases. Skp2 was slightly correlated with Slug and AR in the whole cohort (Rs 0.32 and 0.37, respectively), which was enhanced for both proteins in patients with high Gleason scores (Rs 0.56 and 0.53, respectively) and, in the case of Slug, also in patients with metastasis to lymph nodes (Rs 0.56). Coexpression of Skp2 and Slug was confirmed in prostate cancer tissues by multiplex immunohistochemistry and confocal microscopy. The same relationship between these two proteins was observed in three sets of prostate epithelial cell lines (PC3, DU145, and E2) and their mesenchymal counterparts. Chemical inhibition of Skp2, but not RNA interference, modestly decreased Slug protein in PC3 and its docetaxel-resistant subline PC3 DR12. Importantly, chemical inhibition of Skp2 by MLN4924 upregulated p27 and decreased Slug expression in PC3, PC3 DR12, and LAPC4 cells. Novel treatment strategies targeting Skp2 and Slug by the neddylation blockade may be promising in advanced prostate cancer, as recently documented for other aggressive solid tumors.},
note = {Place: Switzerland},
keywords = {*Protein Processing, Androgen/genetics/metabolism, Antigens, Antineoplastic Agents/pharmacology, Cadherins/genetics/metabolism, CD/genetics/metabolism, Cell Line, Cell Survival/drug effects, Cyclin-Dependent Kinase Inhibitor p27/genetics/metabolism, Cyclopentanes/pharmacology, Docetaxel/pharmacology, Epithelial-Mesenchymal Transition/genetics, Gene Expression Regulation, Humans, Immunohistochemistry, Lymphatic Metastasis, Male, multiplex, NEDD8 Protein/*genetics/metabolism, neddylation, Neoplasm Grading, Neoplastic, PC-3 Cells, Post-Translational, Prostate cancer, Prostate/metabolism/pathology, Prostatic Neoplasms/*genetics/metabolism/pathology, Pyrimidines/pharmacology, Receptors, RNA, S-Phase Kinase-Associated Proteins/antagonists & inhibitors/*genetics/metabolism, Skp2 (S-phase kinase-associated protein 2), Slug, Small Interfering/genetics/metabolism, Snail Family Transcription Factors/*genetics/metabolism, Tumor},
pubstate = {published},
tppubtype = {article}
}
2006
Soucek, Karel; Kamaid, Andrés; Phung, Anh D.; Kubala, Lukás; Bulinski, J. Chloë; Harper, Richart W.; Eiserich, Jason P.
Normal and prostate cancer cells display distinct molecular profiles of alpha-tubulin posttranslational modifications. Journal Article
In: The Prostate, vol. 66, no. 9, pp. 954–965, 2006, ISSN: 0270-4137, (Place: United States).
Abstract | Links | BibTeX | Tags: *Protein Processing, Acetylation, Androgen/analysis, Androgens/physiology, Blotting, Cell Line, Disease Progression, Electrophoresis, Epithelium/chemistry/metabolism/pathology, Fluorescence, Humans, Male, Microscopy, Peptide Synthases/analysis/metabolism, Polyacrylamide Gel, Polyglutamic Acid/analysis, Post-Translational, Prostate/*chemistry/cytology/metabolism, Prostatic Neoplasms/*chemistry/metabolism/pathology, Receptors, Tubulin/*analysis/*metabolism, Tumor, Tyrosine/analysis, Western
@article{soucek_normal_2006,
title = {Normal and prostate cancer cells display distinct molecular profiles of alpha-tubulin posttranslational modifications.},
author = {Karel Soucek and Andrés Kamaid and Anh D. Phung and Lukás Kubala and J. Chloë Bulinski and Richart W. Harper and Jason P. Eiserich},
doi = {10.1002/pros.20416},
issn = {0270-4137},
year = {2006},
date = {2006-06-01},
journal = {The Prostate},
volume = {66},
number = {9},
pages = {954–965},
abstract = {BACKGROUND: Multiple diverse posttranslational modifications of alpha-tubulin such as detyrosination, further cleavage of the penultimate glutamate residue (Delta2-tubulin), acetylation, and polyglutamylation increase the structural and functional diversity of microtubules. METHODS: Herein, we characterized the molecular profile of alpha-tubulin posttranslational modifications in normal human prostate epithelial cells (PrEC), immortalized normal prostate epithelial cells (PZ-HPV-7), androgen-dependent prostate cancer cells (LNCaP), transitional androgen-independent prostate cancer cells (LNCaP-cds and CWR22Rv1), and androgen-independent prostate cancer cells (PC3). RESULTS: Compared to PrEC and PZ-HPV-7 cells, all cancer cells exhibited elevated levels of detyrosinated and polyglutamylated alpha-tubulin, that was paralleled by decreased protein levels of tubulin tyrosine ligase (TTL). In contrast, PrEC and PZ-HPV-7 cells expressed markedly higher levels of Delta2-tubulin. Whereas alpha-tubulin acetylation levels were generally equivalent in all the cell lines, PC3 cells did not display detectable levels of Ac-tubulin. CONCLUSION: These data may reveal novel biomarkers of prostate cancer and new therapeutic targets.},
note = {Place: United States},
keywords = {*Protein Processing, Acetylation, Androgen/analysis, Androgens/physiology, Blotting, Cell Line, Disease Progression, Electrophoresis, Epithelium/chemistry/metabolism/pathology, Fluorescence, Humans, Male, Microscopy, Peptide Synthases/analysis/metabolism, Polyacrylamide Gel, Polyglutamic Acid/analysis, Post-Translational, Prostate/*chemistry/cytology/metabolism, Prostatic Neoplasms/*chemistry/metabolism/pathology, Receptors, Tubulin/*analysis/*metabolism, Tumor, Tyrosine/analysis, Western},
pubstate = {published},
tppubtype = {article}
}