2023
Culig, Zoran; Jolly, Mohit Kumar; Souček, Karel
Editorial: Heterogeneity and plasticity of prostate cancer. Journal Article
In: Frontiers in molecular biosciences, vol. 10, pp. 1228126, 2023, ISSN: 2296-889X, (Place: Switzerland).
Links | BibTeX | Tags: heterogeneity, immunotherapy, oncogenic miRNA, Plasticity, Prostate cancer, therapy resistance, Transcription Factors, tumor-suppressive miRNA
@article{culig_editorial_2023,
title = {Editorial: Heterogeneity and plasticity of prostate cancer.},
author = {Zoran Culig and Mohit Kumar Jolly and Karel Souček},
doi = {10.3389/fmolb.2023.1228126},
issn = {2296-889X},
year = {2023},
date = {2023-01-01},
journal = {Frontiers in molecular biosciences},
volume = {10},
pages = {1228126},
note = {Place: Switzerland},
keywords = {heterogeneity, immunotherapy, oncogenic miRNA, Plasticity, Prostate cancer, therapy resistance, Transcription Factors, tumor-suppressive miRNA},
pubstate = {published},
tppubtype = {article}
}
2020
Muresan, Ximena Maria; Bouchal, Jan; Culig, Zoran; Souček, Karel
Toll-Like Receptor 3 in Solid Cancer and Therapy Resistance. Journal Article
In: Cancers, vol. 12, no. 11, 2020, ISSN: 2072-6694, (Place: Switzerland).
Abstract | Links | BibTeX | Tags: cytokines, dsRNA, Metastasis, therapy resistance, toll-like receptor 3
@article{muresan_toll-like_2020,
title = {Toll-Like Receptor 3 in Solid Cancer and Therapy Resistance.},
author = {Ximena Maria Muresan and Jan Bouchal and Zoran Culig and Karel Souček},
doi = {10.3390/cancers12113227},
issn = {2072-6694},
year = {2020},
date = {2020-11-01},
journal = {Cancers},
volume = {12},
number = {11},
abstract = {Toll-like receptor 3 (TLR3) is a member of the TLR family, which has been extensively studied for its antiviral function. It is highly expressed in the endosomes of antigen-presenting immune cells and epithelial cells. TLR3 binds specifically double-strand RNAs (dsRNAs), leading to the activation of mainly two downstream pathways: the phosphorylation of IRF3, with subsequent production of type I interferon, and the activation of NF-κB, which drives the production of inflammatory cytokines and chemokines. Several studies have demonstrated TLR3 expression in multiple neoplasia types including breast, prostate, and lung cancer. Most studies were focused on the beneficial role of TLR3 activation in tumor cells, which leads to the production of cytotoxic cytokines and interferons and promotes caspase-dependent apoptosis. Indeed, ligands of this receptor were proposed for the treatment of cancer, also in combination with conventional chemotherapy. In contrast to these findings, recent evidence showed a link between TLR3 and tumor progression, metastasis, and therapy resistance. In the present review, we summarize the current knowledge of the mechanisms through which TLR3 can either lead to tumor regression or promote carcinogenesis as well as the potential of TLR-based therapies in resistant cancer.},
note = {Place: Switzerland},
keywords = {cytokines, dsRNA, Metastasis, therapy resistance, toll-like receptor 3},
pubstate = {published},
tppubtype = {article}
}
Toll-like receptor 3 (TLR3) is a member of the TLR family, which has been extensively studied for its antiviral function. It is highly expressed in the endosomes of antigen-presenting immune cells and epithelial cells. TLR3 binds specifically double-strand RNAs (dsRNAs), leading to the activation of mainly two downstream pathways: the phosphorylation of IRF3, with subsequent production of type I interferon, and the activation of NF-κB, which drives the production of inflammatory cytokines and chemokines. Several studies have demonstrated TLR3 expression in multiple neoplasia types including breast, prostate, and lung cancer. Most studies were focused on the beneficial role of TLR3 activation in tumor cells, which leads to the production of cytotoxic cytokines and interferons and promotes caspase-dependent apoptosis. Indeed, ligands of this receptor were proposed for the treatment of cancer, also in combination with conventional chemotherapy. In contrast to these findings, recent evidence showed a link between TLR3 and tumor progression, metastasis, and therapy resistance. In the present review, we summarize the current knowledge of the mechanisms through which TLR3 can either lead to tumor regression or promote carcinogenesis as well as the potential of TLR-based therapies in resistant cancer.
Drápela, Stanislav; Bouchal, Jan; Jolly, Mohit Kumar; Culig, Zoran; Souček, Karel
ZEB1: A Critical Regulator of Cell Plasticity, DNA Damage Response, and Therapy Resistance. Journal Article
In: Frontiers in molecular biosciences, vol. 7, pp. 36, 2020, ISSN: 2296-889X, (Place: Switzerland).
Abstract | Links | BibTeX | Tags: DNA damage response, EMT-epithelial to mesenchymal transition, Plasticity, therapy resistance, ZEB1
@article{drapela_zeb1_2020,
title = {ZEB1: A Critical Regulator of Cell Plasticity, DNA Damage Response, and Therapy Resistance.},
author = {Stanislav Drápela and Jan Bouchal and Mohit Kumar Jolly and Zoran Culig and Karel Souček},
doi = {10.3389/fmolb.2020.00036},
issn = {2296-889X},
year = {2020},
date = {2020-01-01},
journal = {Frontiers in molecular biosciences},
volume = {7},
pages = {36},
abstract = {The predominant way in which conventional chemotherapy kills rapidly proliferating cancer cells is the induction of DNA damage. However, chemoresistance remains the main obstacle to therapy effectivity. An increasing number of studies suggest that epithelial-to-mesenchymal transition (EMT) represents a critical process affecting the sensitivity of cancer cells to chemotherapy. Zinc finger E-box binding homeobox 1 (ZEB1) is a prime element of a network of transcription factors controlling EMT and has been identified as an important molecule in the regulation of DNA damage, cancer cell differentiation, and metastasis. Recent studies have considered upregulation of ZEB1 as a potential modulator of chemoresistance. It has been hypothesized that cancer cells undergoing EMT acquire unique properties that resemble those of cancer stem cells (CSCs). These stem-like cells manifest enhanced DNA damage response (DDR) and DNA repair capacity, self-renewal, or chemoresistance. In contrast, functional experiments have shown that ZEB1 induces chemoresistance regardless of whether other EMT-related changes occur. ZEB1 has also been identified as an important regulator of DDR by the formation of a ZEB1/p300/PCAF complex and direct interaction with ATM kinase, which has been linked to radioresistance. Moreover, ATM can directly phosphorylate ZEB1 and enhance its stability. Downregulation of ZEB1 has also been shown to reduce the abundance of CHK1, an effector kinase of DDR activated by ATR, and to induce its ubiquitin-dependent degradation. In this perspective, we focus on the role of ZEB1 in the regulation of DDR and describe the mechanisms of ZEB1-dependent chemoresistance.},
note = {Place: Switzerland},
keywords = {DNA damage response, EMT-epithelial to mesenchymal transition, Plasticity, therapy resistance, ZEB1},
pubstate = {published},
tppubtype = {article}
}
The predominant way in which conventional chemotherapy kills rapidly proliferating cancer cells is the induction of DNA damage. However, chemoresistance remains the main obstacle to therapy effectivity. An increasing number of studies suggest that epithelial-to-mesenchymal transition (EMT) represents a critical process affecting the sensitivity of cancer cells to chemotherapy. Zinc finger E-box binding homeobox 1 (ZEB1) is a prime element of a network of transcription factors controlling EMT and has been identified as an important molecule in the regulation of DNA damage, cancer cell differentiation, and metastasis. Recent studies have considered upregulation of ZEB1 as a potential modulator of chemoresistance. It has been hypothesized that cancer cells undergoing EMT acquire unique properties that resemble those of cancer stem cells (CSCs). These stem-like cells manifest enhanced DNA damage response (DDR) and DNA repair capacity, self-renewal, or chemoresistance. In contrast, functional experiments have shown that ZEB1 induces chemoresistance regardless of whether other EMT-related changes occur. ZEB1 has also been identified as an important regulator of DDR by the formation of a ZEB1/p300/PCAF complex and direct interaction with ATM kinase, which has been linked to radioresistance. Moreover, ATM can directly phosphorylate ZEB1 and enhance its stability. Downregulation of ZEB1 has also been shown to reduce the abundance of CHK1, an effector kinase of DDR activated by ATR, and to induce its ubiquitin-dependent degradation. In this perspective, we focus on the role of ZEB1 in the regulation of DDR and describe the mechanisms of ZEB1-dependent chemoresistance.