Telomerase and Telomeres in Endometrial Cancer DOI Creative Commons
Rafah Alnafakh, M Adishesh,

Lucy Button

et al.

Frontiers in Oncology, Journal Year: 2019, Volume and Issue: 9

Published: May 17, 2019

Telomeres at the termini of human chromosomes are shortened with each round cell division due to "end replication problem" as well oxidative stress. During carcinogenesis, cells acquire or retain mechanisms maintain telomeres avoid initiation cellular senescence apoptosis and halting by critically short telomeres. The unique reverse transcriptase enzyme complex, telomerase, catalyses maintenance but most somatic do not have sufficient telomerase activity prevent telomere shortening. Tissues high prolonged replicative potential demonstrate adequate erosion, appears be a critical feature (80-90%) epithelial cancers, including endometrial cancer. Endometrial cancers regress in response progesterone which is frequently used treat advanced inhibited progestogens deciphering biology cancer therefore important, targeting (a downstream target progestogens) may provide novel more effective therapeutic avenues. This review aims examine available evidence for role importance

Language: Английский

Molecular Bases of Drug Resistance in Hepatocellular Carcinoma DOI Open Access
José J.G. Marı́n, Rocı́o I.R. Macı́as, María J. Monte

et al.

Cancers, Journal Year: 2020, Volume and Issue: 12(6), P. 1663 - 1663

Published: June 23, 2020

The poor outcome of patients with non-surgically removable advanced hepatocellular carcinoma (HCC), the most frequent type primary liver cancer, is mainly due to high refractoriness this aggressive tumor classical chemotherapy. Novel pharmacological approaches based on use inhibitors tyrosine kinases (TKIs), sorafenib and regorafenib, have provided only a modest prolongation overall survival in these HCC patients. present review an update available information regarding our understanding molecular bases mechanisms chemoresistance (MOC) significant impact response existing tools, which include chemotherapeutic agents, TKIs novel immune-sensitizing strategies. Many more than one hundred genes involved seven MOC been identified as potential biomarkers predict failure treatment, well druggable targets develop strategies aimed at increasing sensitivity treatments.

Language: Английский

Citations

157
Transcriptional Response to Hypoxia: The Role of HIF-1-Associated Co-Regulators DOI Creative Commons

Angelos Yfantis,

Ilias Mylonis, Georgia Chachami

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 798 - 798

Published: March 3, 2023

The Hypoxia Inducible Factor 1 (HIF-1) plays a major role in the cellular response to hypoxia by regulating expression of many genes involved adaptive processes that allow cell survival under low oxygen conditions. Adaptation hypoxic tumor micro-environment is also critical for cancer proliferation and therefore HIF-1 considered valid therapeutical target. Despite huge progress understanding regulation activity levels or oncogenic pathways, way interacts with chromatin transcriptional machinery order activate its target still matter intense investigation. Recent studies have identified several different HIF-1- chromatin-associated co-regulators play important roles general HIF-1, independent levels, as well selection binding sites, promoters genes, which, however, often depends on context. We review here these examine their effect compilation well-characterized direct assess range involvement hypoxia. Delineating mode significance interaction between associated may offer new attractive specific targets anticancer therapy.

Language: Английский

Citations

57
Genetically adjusted PSA levels for prostate cancer screening DOI Creative Commons
Linda Kachuri, Thomas J. Hoffmann, Yu Jiang

et al.

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(6), P. 1412 - 1423

Published: June 1, 2023

Abstract Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. Accounting genetic determinants constitutive, non-cancer-related PSA variation has potential to improve utility. In this study, we discovered 128 genome-wide significant associations ( P < 5 × 10 −8 ) in a multi-ancestry meta-analysis 95,768 men developed polygenic score (PGS that explains 9.61% constitutive variation. We found that, European ancestry, using PGS-adjusted would avoid up 31% negative biopsies but also result 12% fewer patients with cancer, mostly Gleason <7 Genetically adjusted was more predictive aggressive (odds ratio (OR) = 3.44, 6.2 −14 , area under the curve (AUC) 0.755) than unadjusted (OR 3.31, 1.1 −12 AUC 0.738) 106 cases 23,667 controls. Compared PGS alone (AUC 0.712), including genetically improved detection disease 0.786, 7.2 −4 ). Our findings highlight utility incorporating personalized biomarkers screening.

Language: Английский

Citations

47
Role of Rad51 and DNA repair in cancer: A molecular perspective DOI
Erik Laurini, Domenico Marson,

Alice Fermeglia

et al.

Pharmacology & Therapeutics, Journal Year: 2020, Volume and Issue: 208, P. 107492 - 107492

Published: Jan. 27, 2020

Language: Английский

Citations

90
The AAA+ superfamily: a review of the structural and mechanistic principles of these molecular machines DOI Creative Commons
Yousuf A. Khan, K. Ian White, Axel T. Brünger

et al.

Critical Reviews in Biochemistry and Molecular Biology, Journal Year: 2021, Volume and Issue: 57(2), P. 156 - 187

Published: Oct. 11, 2021

ATPases associated with diverse cellular activities (AAA+ proteins) are a superfamily of proteins found throughout all domains life. The hallmark this family is conserved AAA+ domain responsible for range activities. Typically, transduce chemical energy from the hydrolysis ATP into mechanical through conformational change, which can drive variety biological processes. operate in contexts functions including disassembly SNARE proteins, protein quality control, DNA replication, ribosome assembly, and viral replication. This breadth function illustrates both importance health disease emphasizes understanding mechanisms chemo-mechanical transduction. review divided three major portions. First, core fold presented. Next, seven different clades structural details reclassification pertaining to each clade described. Finally, two well-known NSF its close relative p97, reviewed detail.

Language: Английский

Citations

89
Dyskerin: an essential pseudouridine synthase with multifaceted roles in ribosome biogenesis, splicing, and telomere maintenance DOI Open Access

Alexandre Garus,

Chantal Autexier

RNA, Journal Year: 2021, Volume and Issue: 27(12), P. 1441 - 1458

Published: Sept. 23, 2021

Dyskerin and its homologs are ancient conserved enzymes that catalyze the most common post-transcriptional modification found in cells, pseudouridylation. The resulting pseudouridines provide stability to RNA molecules regulate ribosome biogenesis splicing events. does not act independently-it is core component of a protein heterotetramer, which associates with RNAs contain H/ACA motif. variety guide function this ribonucleoprotein (RNP) complex highlights diversity cellular processes dyskerin participates. When associated small nucleolar (sno) RNAs, it regulates ribosomal (r) biogenesis. By interacting Cajal body (sca) targets nuclear (sn) pre-mRNA splicing. As telomerase holoenzyme, binds modulate telomere maintenance. In disease context, malfunction can result multiple detrimental phenotypes. Mutations DKC1, gene encodes dyskerin, cause premature aging syndrome X-linked dyskeratosis congenita (X-DC), still incurable disorder typically leads bone marrow failure. review, we present classical recent findings on essential protein, discussing evolutionary, structural, functional aspects RNP. latest research underscores role plays regulation expression, translation efficiency, maintenance, along impacts defective has aging, cell proliferation, haematopoietic potential, cancer.

Language: Английский

Citations

70
The PAQosome, an R2TP-Based Chaperone for Quaternary Structure Formation DOI
Walid A. Houry, Édouard Bertrand, Benoit Coulombe

et al.

Trends in Biochemical Sciences, Journal Year: 2017, Volume and Issue: 43(1), P. 4 - 9

Published: Dec. 5, 2017

Language: Английский

Citations

78
Toxoplasma Controls Host Cyclin E Expression through the Use of a Novel MYR1-Dependent Effector Protein, HCE1 DOI Creative Commons
Michael W. Panas, Adit Naor,

Alicja M. Cygan

et al.

mBio, Journal Year: 2019, Volume and Issue: 10(2)

Published: April 29, 2019

is an obligate intracellular parasite that establishes a favorable environment in the host cells which it replicates. We have previously reported uses MYR-dependent translocation of dense granule proteins to elicit key set responses related cell cycle, specifically, E2F transcription factor targets, including cyclin E. report here identification novel

Language: Английский

Citations

60
Oxidative Stress Management in Chronic Liver Diseases and Hepatocellular Carcinoma DOI Open Access
Daisuke Uchida, Akinobu Takaki, Atsushi Oyama

et al.

Nutrients, Journal Year: 2020, Volume and Issue: 12(6), P. 1576 - 1576

Published: May 28, 2020

Chronic viral hepatitis B and C non-alcoholic fatty liver disease (NAFLD) have been widely acknowledged to be the leading causes of cirrhosis hepatocellular carcinoma. As anti-viral treatment progresses, impact NAFLD is increasing. can coexist with chronic exacerbate its progression. Oxidative stress has recognized as a progression-related cancer-initiating response. However, there are still many unresolved issues concerning oxidative stress, such correlation between natural history promising protocols. Recent findings indicate that also an anti-cancer response necessary kill cancer cells. might therefore should down regulated in pre-cancerous stage patients risk factors for cancer, while it cell not post-cancerous stage, especially using agents. Antioxidant nutrients administered carefully according patients' status. In this review, we will highlight these paradoxical effects diseases, pre- post-carcinogenesis.

Language: Английский

Citations

59
The transcriptional coactivator RUVBL2 regulates Pol II clustering with diverse transcription factors DOI Creative Commons
Hui Wang, Boyuan Li,

Linyu Zuo

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Sept. 28, 2022

RNA polymerase II (Pol II) apparatuses are compartmentalized into transcriptional clusters. Whether protein factors control these clusters remains unknown. In this study, we find that the ATPase-associated with diverse cellular activities (AAA + ) ATPase RUVBL2 co-occupies promoters Pol and various transcription factors. interacts unphosphorylated in chromatin to promote RPB1 carboxy-terminal domain (CTD) clustering initiation. Rapid depletion of leads a decrease number inhibits nascent synthesis, tethering an active promoter enhances at promoter. We also identify target genes directly linked RUVBL2-Pol axis. Many hallmarks cancers encode proteins functions. Our results demonstrate emerging activity for regulating cluster formation nucleus.

Language: Английский

Citations

30