LIVIVO - Search results -

Search results

Result 1 - 10 of total 48

Search options

Article ; Online: Harnessing mitochondrial metabolism and drug resistance in non-small cell lung cancer and beyond by blocking heat-shock proteins.

Parma, Beatrice / Wurdak, Heiko / Ceppi, Paolo

Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy

2022 Volume 65, Page(s) 100888

Abstract: Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) being the predominant histological subtype. Despite the emergence of targeted and immune-based therapies that have considerably improved the ... ...

Abstract	Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) being the predominant histological subtype. Despite the emergence of targeted and immune-based therapies that have considerably improved the clinical outcomes of selected patients, the overall NSCLC survival rate remains poor. NSCLC patients experience clinical relapse mainly because of chemoresistance. One promising therapeutic approach is targeting specific molecular vulnerabilities that are associated with the metabolic reprogramming of cancer cells. This strategy relies on evidence that cancer cells rewire their metabolism to sustain their uncontrolled growth as well as invasive and metastatic properties, promoting adaptive resistance to chemo-radiotherapy. A critical component of this malignant transformation is the increased dependency on high levels of heat shock proteins (HSPs), which support the elevated protein folding demand and quality control of misfolded oncoproteins. Here, we provide an overview of the literature on metabolism reprogramming, deregulation of mitochondrion and on the role of HSPs in promoting malignancy in lung and other cancer types. A particular focus is dedicated to the role of mitochondrial HSP60 (HSPD1) in NSCLC metabolism and drug resistance for the potential development of new resistance-defying anti-HSP drugs.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Heat-Shock Proteins/genetics ; Heat-Shock Proteins/metabolism ; Heat-Shock Proteins/therapeutic use ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Mitochondria ; Drug Resistance
Chemical Substances	Heat-Shock Proteins
Language	English
Publishing date	2022-10-28
Publishing country	Scotland
Document type	Journal Article ; Review
ZDB-ID	1474513-6
ISSN	1532-2084 ; 1368-7646
ISSN (online)	1532-2084
ISSN	1368-7646
DOI	10.1016/j.drup.2022.100888
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5099: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: A non-proliferative role of pyrimidine metabolism in cancer.

Siddiqui, Aarif / Ceppi, Paolo

Molecular metabolism

2020 Volume 35, Page(s) 100962

Abstract: Background: Nucleotide metabolism is a critical pathway that generates purine and pyrimidine molecules for DNA replication, RNA synthesis, and cellular bioenergetics. Increased nucleotide metabolism supports uncontrolled growth of tumors and is a ... ...

Abstract	Background: Nucleotide metabolism is a critical pathway that generates purine and pyrimidine molecules for DNA replication, RNA synthesis, and cellular bioenergetics. Increased nucleotide metabolism supports uncontrolled growth of tumors and is a hallmark of cancer. Agents inhibiting synthesis and incorporation of nucleotides in DNA are widely used as chemotherapeutics to reduce tumor growth, cause DNA damage, and induce cell death. Thus, the research on nucleotide metabolism in cancer is primarily focused on its role in cell proliferation. However, in addition to proliferation, the role of purine molecules is established as ligands for purinergic signals. However, so far, the role of the pyrimidines has not been discussed beyond cell growth. Scope of the review: In this review we present the key evidence from recent pivotal studies supporting the notion of a non-proliferative role for pyrimidine metabolism (PyM) in cancer, with a special focus on its effect on differentiation in cancers from different origins. Major conclusion: In leukemic cells, the pyrimidine catabolism induces terminal differentiation toward monocytic lineage to check the aberrant cell proliferation, whereas in some solid tumors (e.g., triple negative breast cancer and hepatocellular carcinoma), catalytic degradation of pyrimidines maintains the mesenchymal-like state driven by epithelial-to-mesenchymal transition (EMT). This review further broadens this concept to understand the effect of PyM on metastasis and, ultimately, delivers a rationale to investigate the involvement of the pyrimidine molecules as oncometabolites. Overall, understanding the non-proliferative role of PyM in cancer will lead to improvement of the existing antimetabolites and to development of new therapeutic options.
MeSH term(s)	Animals ; Cell Differentiation ; Cell Proliferation ; Disease Progression ; Drug Resistance, Neoplasm ; Epithelial-Mesenchymal Transition ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Metastasis ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplastic Stem Cells/metabolism ; Pyrimidines/metabolism
Chemical Substances	Pyrimidines ; pyrimidine (K8CXK5Q32L)
Language	English
Publishing date	2020-02-13
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2708735-9
ISSN	2212-8778 ; 2212-8778
ISSN (online)	2212-8778
ISSN	2212-8778
DOI	10.1016/j.molmet.2020.02.005
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Targeting EMT in Cancer with Repurposed Metabolic Inhibitors.

Ramesh, Vignesh / Brabletz, Thomas / Ceppi, Paolo

Trends in cancer

2020 Volume 6, Issue 11, Page(s) 942–950

Abstract: Epithelial-to-mesenchymal transition (EMT) determines the most lethal features of cancer, metastasis formation and chemoresistance, and therefore represents an attractive target in oncology. However, direct targeting of EMT effector molecules is, in most ...

Abstract	Epithelial-to-mesenchymal transition (EMT) determines the most lethal features of cancer, metastasis formation and chemoresistance, and therefore represents an attractive target in oncology. However, direct targeting of EMT effector molecules is, in most cases, pharmacologically challenging. Since emerging research has highlighted the distinct metabolic circuits involved in EMT, we propose the use of metabolism-specific inhibitors, FDA approved or under clinical trials, as a drug repurposing approach to target EMT in cancer. Metabolism-inhibiting drugs could be coupled with standard chemo- or immunotherapy to combat EMT-driven resistant and aggressive cancers.
MeSH term(s)	Antimetabolites, Antineoplastic/pharmacology ; Antimetabolites, Antineoplastic/therapeutic use ; Cell Line, Tumor ; Drug Discovery ; Drug Repositioning ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Epithelial-Mesenchymal Transition/drug effects ; Epithelial-Mesenchymal Transition/genetics ; Humans ; Metabolic Networks and Pathways/drug effects ; Metabolic Networks and Pathways/genetics ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/pathology ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/genetics
Chemical Substances	Antimetabolites, Antineoplastic
Language	English
Publishing date	2020-07-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2852626-0
ISSN	2405-8025 ; 2405-8033 ; 2405-8033
ISSN (online)	2405-8025 ; 2405-8033
ISSN	2405-8033
DOI	10.1016/j.trecan.2020.06.005
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Details ▾
- Full text online
- Order with fees

Article ; Online: Down-Regulation of CK2α Leads toUp-Regulation of the Cyclin-Dependent Kinase Inhibitor p27

Guerra, Barbara / Dembic, Maja / Siddiqui, Mohammad A / Dominguez, Isabel / Ceppi, Paolo / Andresen, Brage S

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology

2020 Volume 54, Issue 6, Page(s) 1177–1198

Abstract: Background/aims: Compelling evidence indicates that CK2α, which is one of the two catalytic isoforms of protein kinase CK2, is required for cell viability and plays an important role in cell proliferation and differentiation. While much is known on CK2 ... ...

Abstract	Background/aims: Compelling evidence indicates that CK2α, which is one of the two catalytic isoforms of protein kinase CK2, is required for cell viability and plays an important role in cell proliferation and differentiation. While much is known on CK2 in the context of disease states, particularly cancer, its critical role in non-cancerous cell growth has not been extensively investigated. Methods: In the present study, we have employed a cell line derived from rat heart with inducible down-regulation of CK2α and CK2α-knockout mouse tissue to identify CK2-mediated molecular mechanisms regulating cell growth. For this, we have performed Incucyte® live-cell analysis and applied flow cytometry, western blot, immunoprecipitation, immunohistochemistry, RT-qPCR and luciferase-based methods. Results: Here, we show that lack of CK2α results in significantly delayed cell cycle progression through G1, inhibition of cyclin E-CDK2 complex, decreased phosphorylation of Rb protein at S795, and inactivation of E2F transcription factor. These events are accompanied by nuclear accumulation and up-regulation of the cyclin-dependent kinase inhibitor p27 Conclusion: Taken together, our study sheds light on the molecular mechanisms controlling cell cycle progression through G1 phase when myoblasts proliferation potential is impaired by CK2α depletion. Our results suggest that elevated levels of p27
MeSH term(s)	Animals ; Casein Kinase II/biosynthesis ; Cell Line ; Cyclin-Dependent Kinase Inhibitor p27/biosynthesis ; Cyclin-Dependent Kinase Inhibitor p27/genetics ; Down-Regulation ; G1 Phase ; Gene Expression Regulation, Enzymologic ; Myoblasts/metabolism ; Rats ; S Phase ; Up-Regulation
Chemical Substances	Cdkn1b protein, rat ; Cyclin-Dependent Kinase Inhibitor p27 (147604-94-2) ; Casein Kinase II (EC 2.7.11.1)
Language	English
Publishing date	2020-11-20
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1067572-3
ISSN	1421-9778 ; 1015-8987
ISSN (online)	1421-9778
ISSN	1015-8987
DOI	10.33594/000000308
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3160: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma.

Ramesh, Vignesh / Gollavilli, Paradesi Naidu / Pinna, Luisa / Siddiqui, Mohammad Aarif / Turtos, Adriana Martinez / Napoli, Francesca / Antonelli, Yasmin / Leal-Egaña, Aldo / Havelund, Jesper Foged / Jakobsen, Simon Toftholm / Boiteux, Elisa Le / Volante, Marco / Faergeman, Nils Joakim / Jensen, Ole N / Siersbaek, Rasmus / Somyajit, Kumar / Ceppi, Paolo

EMBO molecular medicine

2023 Volume 15, Issue 12, Page(s) e17836

Abstract: The epithelial-to-mesenchymal transition (EMT) plays a central role in the development of cancer metastasis and resistance to chemotherapy. However, its pharmacological treatment remains challenging. Here, we used an EMT-focused integrative functional ... ...

Abstract	The epithelial-to-mesenchymal transition (EMT) plays a central role in the development of cancer metastasis and resistance to chemotherapy. However, its pharmacological treatment remains challenging. Here, we used an EMT-focused integrative functional genomic approach and identified an inverse association between short-chain fatty acids (propionate and butanoate) and EMT in non-small cell lung cancer (NSCLC) patients. Remarkably, treatment with propionate in vitro reinforced the epithelial transcriptional program promoting cell-to-cell contact and cell adhesion, while reducing the aggressive and chemo-resistant EMT phenotype in lung cancer cell lines. Propionate treatment also decreased the metastatic potential and limited lymph node spread in both nude mice and a genetic NSCLC mouse model. Further analysis revealed that chromatin remodeling through H3K27 acetylation (mediated by p300) is the mechanism underlying the shift toward an epithelial state upon propionate treatment. The results suggest that propionate administration has therapeutic potential in reducing NSCLC aggressiveness and warrants further clinical testing.
MeSH term(s)	Humans ; Animals ; Mice ; Lung Neoplasms/genetics ; Carcinoma, Non-Small-Cell Lung/genetics ; Propionates/pharmacology ; Propionates/therapeutic use ; Mice, Nude ; Cell Line, Tumor ; Lung/metabolism ; Epithelial-Mesenchymal Transition ; Gene Expression Regulation, Neoplastic ; Cell Movement
Chemical Substances	Propionates
Language	English
Publishing date	2023-09-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2467145-9
ISSN	1757-4684 ; 1757-4676
ISSN (online)	1757-4684
ISSN	1757-4676
DOI	10.15252/emmm.202317836
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6784: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: 3D hydrogel-based microcapsules as an in vitro model to study tumorigenicity, cell migration and drug resistance.

Ertekin, Özlem / Monavari, Mahshid / Krüger, René / Fuentes-Chandía, Miguel / Parma, Beatrice / Letort, Gaelle / Tripal, Philipp / Boccaccini, Aldo R / Bosserhoff, Anja K / Ceppi, Paolo / Kappelmann-Fenzl, Melanie / Leal-Egaña, Aldo

Acta biomaterialia

2022 Volume 142, Page(s) 208–220

Abstract: In this work, we analyzed the reliability of alginate-gelatin microcapsules as artificial tumor model. These tumor-like scaffolds are characterized by their composition and stiffness (∼25 kPa), and their capability to restrict -but not hinder- cell ... ...

Abstract	In this work, we analyzed the reliability of alginate-gelatin microcapsules as artificial tumor model. These tumor-like scaffolds are characterized by their composition and stiffness (∼25 kPa), and their capability to restrict -but not hinder- cell migration, proliferation and release from confinement. Hydrogel-based microcapsules were initially utilized to detect differences in mechano-sensitivity between MCF7 and MDA-MB-231 breast cancer cells, and the endothelial cell line EA.hy926. Additionally, we used RNA-seq and transcriptomic methods to determine how the culture strategy (i.e. 2D v/s 3D) may pre-set the expression of genes involved in multidrug resistance, being then validated by performing cytotoxicological tests and assays of cell morphology. Our results show that both breast cancer cells can generate elongated multicellular spheroids inside the microcapsules, prior being released (mimicking intravasation stages), a behavior which was not observed in endothelial cells. Further, we demonstrate that cells isolated from 3D scaffolds show resistance to cisplatin, a process which seems to be strongly influenced by mechanical stress, instead of hypoxia. We finally discuss the role played by aneuploidy in malignancy and resistance to anticancer drugs, based on the increased number of polynucleated cells found within these microcapsules. Overall, our outcomes demonstrate that alginate-gelatin microcapsules represent a simple, yet very accurate tumor-like model, enabling us to mimic the most relevant malignant hints described in vivo, suggesting that confinement and mechanical stress need to be considered when studying pathogenicity and drug resistance of cancer cells in vitro. STATEMENT OF SIGNIFICANCE: In this work, we analyzed the reliability of alginate-gelatin microcapsules as an artificial tumor model. These scaffolds are characterized by their composition, elastic properties, and their ability to restrict cell migration, proliferation, and release from confinement. Our results demonstrate four novel outcomes: (i) studying cell migration and proliferation in 3D enabled discrimination between malignant and non-pathogenic cells, (ii) studying the cell morphology of cancer aggregates entrapped in alginate-gelatin microcapsules enabled determination of malignancy degree in vitro, (iii) determination that confinement and mechanical stress, instead of hypoxia, are required to generate clones resistant to anticancer drugs (i.e. cisplatin), and (iv) evidence that resistance to anticancer drugs could be due to the presence of polynucleated cells localized inside polymer-based artificial tumors.
MeSH term(s)	Alginates/pharmacology ; Antineoplastic Agents/pharmacology ; Breast Neoplasms ; Capsules ; Cell Movement ; Cisplatin/pharmacology ; Drug Resistance ; Endothelial Cells ; Female ; Gelatin/pharmacology ; Humans ; Hydrogels/pharmacology ; Hypoxia ; Reproducibility of Results
Chemical Substances	Alginates ; Antineoplastic Agents ; Capsules ; Hydrogels ; Gelatin (9000-70-8) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2022-02-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2022.02.010
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: The role of miR-200b/c in balancing EMT and proliferation revealed by an activity reporter.

Gollavilli, Paradesi Naidu / Parma, Beatrice / Siddiqui, Aarif / Yang, Hai / Ramesh, Vignesh / Napoli, Francesca / Schwab, Annemarie / Natesan, Ramakrishnan / Mielenz, Dirk / Asangani, Irfan Ahmed / Brabletz, Thomas / Pilarsky, Christian / Ceppi, Paolo

Oncogene

2021 Volume 40, Issue 12, Page(s) 2309–2322

Abstract: Since their discovery, microRNAs (miRNAs) have been widely studied in almost every aspect of biology and medicine, leading to the identification of important gene regulation circuits and cellular mechanisms. However, investigations are generally focused ... ...

Abstract	Since their discovery, microRNAs (miRNAs) have been widely studied in almost every aspect of biology and medicine, leading to the identification of important gene regulation circuits and cellular mechanisms. However, investigations are generally focused on the analysis of their downstream targets and biological functions in overexpression and knockdown approaches, while miRNAs endogenous levels and activity remain poorly understood. Here, we used the cellular plasticity-regulating process of epithelial-to-mesenchymal transition (EMT) as a model to show the efficacy of a fluorescent sensor to separate cells with distinct EMT signatures, based on miR-200b/c activity. The system was further combined with a CRISPR-Cas9 screening platform to unbiasedly identify miR-200b/c upstream regulating genes. The sensor allows to infer miRNAs fundamental biological properties, as profiling of sorted cells indicated miR-200b/c as a molecular switch between EMT differentiation and proliferation, and suggested a role for metabolic enzymes in miR-200/EMT regulation. Analysis of miRNAs endogenous levels and activity for in vitro and in vivo applications could lead to a better understanding of their biological role in physiology and disease.
MeSH term(s)	Cell Differentiation/genetics ; Cell Plasticity/genetics ; Cell Proliferation/genetics ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; Epithelial-Mesenchymal Transition/genetics ; HCT116 Cells ; Humans ; MicroRNAs/genetics
Chemical Substances	MIRN200 microRNA, human ; MicroRNAs
Language	English
Publishing date	2021-03-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-021-01708-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2218: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Roflumilast inhibits tumor growth and migration in STK11/LKB1 deficient pancreatic cancer.

Zhang, Shuman / Yun, Duo / Yang, Hao / Eckstein, Markus / Elbait, Gihan Daw / Zhou, Yaxing / Lu, Yanxi / Yang, Hai / Zhang, Jinping / Dörflein, Isabella / Britzen-Laurent, Nathalie / Pfeffer, Susanne / Stemmler, Marc P / Dahl, Andreas / Mukhopadhyay, Debabrata / Chang, David / He, Hang / Zeng, Siyuan / Lan, Bin /

Frey, Benjamin / Hampel, Chuanpit / Lentsch, Eva / Gollavilli, Paradesi Naidu / Büttner, Christian / Ekici, Arif B / Biankin, Andrew / Schneider-Stock, Regine / Ceppi, Paolo / Grützmann, Robert / Pilarsky, Christian

Cell death discovery

2024 Volume 10, Issue 1, Page(s) 124

Abstract: Pancreatic cancer is a malignant tumor of the digestive system. It is highly aggressive, easily metastasizes, and extremely difficult to treat. This study aimed to analyze the genes that might regulate pancreatic cancer migration to provide an essential ... ...

Abstract	Pancreatic cancer is a malignant tumor of the digestive system. It is highly aggressive, easily metastasizes, and extremely difficult to treat. This study aimed to analyze the genes that might regulate pancreatic cancer migration to provide an essential basis for the prognostic assessment of pancreatic cancer and individualized treatment. A CRISPR knockout library directed against 915 murine genes was transfected into TB 32047 cell line to screen which gene loss promoted cell migration. Next-generation sequencing and PinAPL.py- analysis was performed to identify candidate genes. We then assessed the effect of serine/threonine kinase 11 (STK11) knockout on pancreatic cancer by wound-healing assay, chick agnosia (CAM) assay, and orthotopic mouse pancreatic cancer model. We performed RNA sequence and Western blotting for mechanistic studies to identify and verify the pathways. After accelerated Transwell migration screening, STK11 was identified as one of the top candidate genes. Further experiments showed that targeted knockout of STK11 promoted the cell migration and increased liver metastasis in mice. Mechanistic analyses revealed that STK11 knockout influences blood vessel morphogenesis and is closely associated with the enhanced expression of phosphodiesterases (PDEs), especially PDE4D, PDE4B, and PDE10A. PDE4 inhibitor Roflumilast inhibited STK11-KO cell migration and tumor size, further demonstrating that PDEs are essential for STK11-deficient cell migration. Our findings support the adoption of therapeutic strategies, including Roflumilast, for patients with STK11-mutated pancreatic cancer in order to improve treatment efficacy and ultimately prolong survival.
Language	English
Publishing date	2024-03-09
Publishing country	United States
Document type	Journal Article
ISSN	2058-7716
ISSN	2058-7716
DOI	10.1038/s41420-024-01890-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: CD95 is part of a let-7/p53/miR-34 regulatory network.

Hau, Annika / Ceppi, Paolo / Peter, Marcus E

PloS one

2012 Volume 7, Issue 11, Page(s) e49636

Abstract: The death receptor CD95 (APO-1/Fas) mediates apoptosis induction upon ligation by its cognate ligand CD95L. Two types of CD95 signaling pathways have been identified, which are characterized by the absence (Type I) or presence (Type II) of mitochondrial ... ...

Abstract	The death receptor CD95 (APO-1/Fas) mediates apoptosis induction upon ligation by its cognate ligand CD95L. Two types of CD95 signaling pathways have been identified, which are characterized by the absence (Type I) or presence (Type II) of mitochondrial involvement. Micro(mi)RNAs are small noncoding RNAs that negatively regulate gene expression. They are important regulators of differentiation processes and are found frequently deregulated in many human cancers. We recently showed that Type I cells express less of the differentiation marker miRNA let-7 and, hence, likely represent more advanced tumor cells than the let-7 high expressing Type II cells. We have now identified miR-34a as a selective marker for cells that are sensitive to CD95-mediated apoptosis. Both CD95 and miR-34a are p53 target genes, and consequently, both the sensitivity of cancer cells to CD95-mediated apoptosis and the ability to respond to p53 mediated DNA genotoxic stress are linked. Interestingly, while miR-34a was found to positively correlate with the ability of cells to respond to genotoxic stress, let-7 was negatively correlated. The expression level of CD95 inversely correlated with the expression of let-7 suggesting regulation of let-7 expression by CD95. To test a link between p53 and miR-34a, we altered the expression of CD95. This affected the ability of cells to activate p53 and to regulate miR-34a. Our data point to a novel regulatory network comprising p53, CD95, let-7, and miR-34a that affects cancer cell survival, differentiation, and sensitivity to apoptotic signals. The possible relevance of this regulatory network for cancer stem cells is discussed.
MeSH term(s)	Apoptosis/genetics ; Cell Line, Tumor ; DNA Damage ; Epistasis, Genetic ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Gene Silencing ; Humans ; MicroRNAs/genetics ; Signal Transduction ; Transcription, Genetic ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; fas Receptor/genetics ; fas Receptor/metabolism
Chemical Substances	MIRN34 microRNA, human ; MicroRNAs ; Tumor Suppressor Protein p53 ; fas Receptor ; mirnlet7 microRNA, human
Language	English
Publishing date	2012-11-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0049636
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Characterization and diagnostic application of genomic

Krumbholz, Manuela / Woessmann, Wilhelm / Zierk, Jakob / Seniuk, David / Ceppi, Paolo / Zimmermann, Martin / Singh, Vijay Kumar / Metzler, Markus / Damm-Welk, Christine

Oncotarget

2018 Volume 9, Issue 41, Page(s) 26543–26555

Abstract: Nucleophosmin-anaplastic lymphoma ... ...

Abstract	Nucleophosmin-anaplastic lymphoma kinase
Language	English
Publishing date	2018-05-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.25489
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito