scholarly journals The Involvement ofNRF2in Lung Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Alison K. Bauer ◽  
Thomas Hill ◽  
Carla-Maria Alexander
Keyword(s):  
Lung Cancer ◽  
Mouse Models ◽  
Stress Responses ◽  
Loss Of Function ◽  
Mutation Status ◽  
Activating Mutations ◽  
Cellular Stress Responses ◽  
Xenograft Models ◽  
Pulmonary Neoplasia

Nuclear factor, erythroid-derived 2, like 2 (NRF2) is a key regulator of antioxidants and cellular stress responses. The role ofNRF2in pulmonary neoplasia, a diverse disease for which few biomarkers exist, is complicated and appears to depend on several main factors including the existence of activating mutations inNRF2and/or loss of function mutations inKEAP1and the stage of carcinogenesis studied, particularly in the mouse models tested. Therapeutic strategies for lung cancer targetingNRF2have observed mixed results, both anti- and protumorigenic effects; however, these differences seem to reflect the mutation status ofNRF2orKEAP1. In this paper, we will discuss the studies on humanNRF2and the mechanisms proposed, several mouse models using various mice deficient inNRF2, as well as xenograft models, and the chemotherapeutic strategies using theNRF2pathway.

scholarly journals Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 99
Author(s):  
Shweta Devi ◽  
Vijay Kumar ◽  
Sandeep Kumar Singh ◽  
Ashish Kant Dubey ◽  
Jong-Joo Kim
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Neurodegenerative Disorders ◽  
Cell Damage ◽  
Cellular Stress ◽  
Clinical Manifestations ◽  
Cellular Stress Response ◽  
Dramatic Rise ◽  
Cellular Stress Responses

Neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are the most concerning disorders due to the lack of effective therapy and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and endoplasmic reticulum (ER)-stress, which combats with stress conditions. Environmental stress/toxicity weakened the cellular stress response which results in cell damage. Small molecules, such as flavonoids, could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways, such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the potential role of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.

scholarly journals Dependency of human and murine LKB1-inactivated lung cancer on aberrant CRTC-CREB activation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Xin Zhou ◽  
Jennifer W Li ◽  
Zirong Chen ◽  
Wei Ni ◽  
Xuehui Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Expression Patterns ◽  
Direct Proof ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Loss Of Function ◽  
Creb Activation ◽  
Interaction Interface ◽  
Lkb1 Tumor Suppressor

Lung cancer with loss-of-function of the LKB1 tumor suppressor is a common aggressive subgroup with no effective therapies. LKB1-deficiency induces constitutive activation of cAMP/CREB-mediated transcription by a family of three CREB-regulated transcription coactivators (CRTC1-3). However, the significance and mechanism of CRTC activation in promoting the aggressive phenotype of LKB1-null cancer remain poorly characterized. Here we observed overlapping CRTC expression patterns and mild growth phenotypes of individual CRTC-knockouts in lung cancer, suggesting functional redundancy of CRTC1-3. We consequently designed a dominant-negative mutant (dnCRTC) to block all three CRTCs to bind and co-activate CREB. Expression of dnCRTC efficiently inhibited the aberrantly activated cAMP/CREB-mediated oncogenic transcriptional program induced by LKB1-deficiency, and specifically blocked the growth of human and murine LKB1-inactivated lung cancer. Collectively, this study provides direct proof for an essential role of the CRTC-CREB activation in promoting the malignant phenotypes of LKB1-null lung cancer and proposes the CRTC-CREB interaction interface as a novel therapeutic target.

scholarly journals HIRA contributes to zygote formation in mice and is implicated in human 1PN zygote phenotype

Reproduction ◽  
2021 ◽  
Author(s):  
Rowena Smith ◽  
Susan J Pickering ◽  
Anna Kopakaki ◽  
Kj Thong ◽  
Richard A Anderson ◽  
...  
Keyword(s):  
Mouse Models ◽  
Sperm Chromatin ◽  
Zygote Formation ◽  
Loss Of Function ◽  
Phenotype Correlation ◽  
Male Pronucleus ◽  
Histone H3.3 ◽  
Chromatin Reprogramming ◽  
Histone Exchange

Elucidating the mechanisms underpinning fertilisation is essential to optimising IVF procedures. One of the critical steps involves paternal chromatin reprogramming, in which compacted sperm chromatin packed by protamines is removed by oocyte factors and new histones, including histone H3.3, are incorporated. HIRA is the main H3.3 chaperone governing this protamine-to-histone exchange. Failure of this step results in abnormally fertilised zygotes containing only 1 pronucleus (1PN), in contrast to normal two-pronuclei (2PN) zygotes. 1PN zygotes are frequently observed in IVF treatments, but the genotype-phenotype correlation remains elusive. We investigated the maternal functions of two other molecules of the Hira complex, Cabin1 and Ubn1, in mouse. Loss-of-function Cabin1 and Ubn1 mouse models were developed: their zygotes displayed an abnormal 1PN zygote phenotype. We then studied human 1PN zygotes and found that the HIRA complex was absent in 1PN zygotes that lacked the male pronucleus. This shows that the role of the HIRA complex in male pronucleus formation potentially has coherence from mice to humans. Furthermore, rescue experiments in mouse showed that the abnormal 1PN phenotype derived from Hira mutants could be resolved by overexpression of HIRA. We have demonstrated that HIRA complex regulates male pronucleus formation in mice and is implicated in humans, that both CABIN1 and UBN1 components of the HIRA complex are equally essential for male pronucleus formation, and that rescue is feasible.

scholarly journals Usp14 is required for spermatogenesis and ubiquitin stress responses in Drosophila melanogaster

2019 ◽  
Author(s):  
Levente Kovács ◽  
Ágota Nagy ◽  
Margit Pál ◽  
Peter Deák
Keyword(s):  
Male Sterility ◽  
Stress Responses ◽  
Expression Patterns ◽  
Loss Of Function ◽  
Wild Type ◽  
Cellular Processes ◽  
Protein Conjugates ◽  
Covalently Linked ◽  
Mutant Phenotypes

ABSTRACTDeubiquitinating (DUB) enzymes free covalently linked ubiquitins from ubiquitin-ubiquitin and ubiquitin-protein conjugates, and thereby maintain the equilibrium between free and conjugated ubiquitins and regulate ubiquitin-mediated cellular processes. The present genetic analyses of mutant phenotypes demonstrate that loss of Usp14 function results in male sterility, with defects in spermatid individualization and reduced testicular free monoubiquitin levels. These phenotypes were rescued by germline specific overexpression of wild type Usp14. Synergistic genetic interactions with Ubi-p63E and cycloheximide sensitivity suggest that ubiquitin shortage is a primary cause of male sterility. In addition, Usp14 is predominantly expressed in testes in Drosophila, and differential expression patterns may be causative of testis-specific loss of function Usp14 phenotypes. Collectively, these results suggest a major role of Usp14 in maintaining normal steady state free monoubiquitin levels during the later stages of Drosophila spermatogenesis.

EBAG9 is a tumor‐promoting and prognostic factor for bladder cancer.

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Bladder Cancer ◽  
Immunohistochemical Study ◽  
Tumor Formation ◽  
Loss Of Function ◽  
Xenograft Models ◽  
Prostate Cancers ◽  
And Migration

Upregulation of EBAG9 expression has been observed in severalmalignant tumors such as advanced breast and prostate cancers,indicating that EBAG9 may contribute to tumor proliferation. Inthe present study, we assess the role of EBAG9 in bladder cancer.We generated human bladder cancer EJ cells stably expressingFLAG-tagged EBAG9 (EJ-EBAG9) or empty vector (EJ-vector),and investigated whether EBAG9 overexpression modulates cellgrowth and migration in vitro as well as the in vivo tumor formationof EJ transfectants in xenograft models of BALB/c nude mice.EBAG9 overexpression promoted EJ cell migration, while theeffect of EBAG9 to cultured cell growth was rather minimal.Tumorigenic experiments in nude mice showed that the size of EJEBAG9-derived tumors was significantly larger than EJ-vectorderivedtumors. Loss-of-function study for EBAG9 using smallinterfering RNA (siRNA) in xenografts with parental EJ cellsshowed that the intra-tumoral injection of EBAG9 siRNA markedlyreduced the EJ tumor formation compared with controlsiRNA. Furthermore, immunohistochemical study for EBAG9expression was performed in 60 pathological bladder cancer specimens.Intense and diffuse cytoplasmic immunostaining wasobserved in 45% of the bladder cancer cases. Positive EBAG9immunoreactivity was closely correlated with poor prognosis ofthe patients (p 5 0.0001) and it was an independent prognosticpredictor for disease-specific survival in multivariate analysis(p 5 0.003). Our results indicate that EBAG9 would be a crucialregulator of tumor progression and a potential prognostic markerfor bladder cancer.

The Role of PARP-1 in Host-Pathogen Interaction and Cellular Stress Responses

2015 ◽  
Vol 25 (2) ◽  
pp. 175-190 ◽  
Author(s):  
Hui Li ◽  
Qiming Li ◽  
Wu Li ◽  
Longxiang Xie ◽  
Mingliang Zhou ◽  
...  
Keyword(s):  
Stress Responses ◽  
Cellular Stress ◽  
Host Pathogen Interaction ◽  
Host Pathogen ◽  
Cellular Stress Responses ◽  
Parp 1

Role of [18F]FDG PET in prediction of KRAS and EGFR mutation status in patients with advanced non-small-cell lung cancer

2014 ◽  
Vol 41 (11) ◽  
pp. 2058-2065 ◽  
Author(s):  
Carlos Caicedo ◽  
Maria Jose Garcia-Velloso ◽  
Maria Dolores Lozano ◽  
Tania Labiano ◽  
Carmen Vigil Diaz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Fdg Pet ◽  
Egfr Mutation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mutation Status ◽  
18F Fdg
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