Oxygen and cancer

2019 ◽  
pp. 255-269
Author(s):  
Adrian L. Harris ◽  
Margaret Ashcroft
Keyword(s):  
Cellular Response ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Solid Tumours ◽  
Adaptive Responses ◽  
Tumour Vasculature ◽  
Evolutionarily Conserved ◽  
And Function ◽  
Different Cell Types ◽  
The Impact

Oxygen is required for most multicellular, aerobic organisms to survive and function. The vasculature provides the conduit for delivering oxygen via haemoglobin in the blood to organs, tissues, and cells. In diseases such as cancer, low tissue oxygenation or hypoxia occurs in solid tumours because of an inadequate supply of oxygen due to aberrant tumour vasculature. Hypoxia is a key feature of most solid tumours and underlies many of the processes associated with how cancer progresses; including tumour cell survival and proliferation, genetic instability, immune responses, angiogenesis, invasion and metastasis, and metabolic adaptive responses. Solid tumours contain several different cell types that respond to hypoxia within the tumour microenvironment. Hypoxia-inducible factors (HIFs) are a highly evolutionarily conserved family of dimeric transcription factors that are central to mediating the cellular response to hypoxia by regulating the expression of a diverse array of targets. Hypoxia and HIF activation is associated with treatment failure, resistance, and poor clinical outcomes. This chapter will provide an overview of the role of hypoxia in cancer, outline the methods used to measure hypoxia clinically, and discuss the impact of hypoxia on current front-line therapies being used to treat cancer.

scholarly journals Building the right centriole for each cell type

2017 ◽  
Vol 217 (3) ◽  
pp. 823-835 ◽  
Author(s):  
Jadranka Loncarek ◽  
Mónica Bettencourt-Dias
Keyword(s):  
Cell Cycle Progression ◽  
Cell Types ◽  
Cell Type ◽  
Cycle Progression ◽  
Single Organism ◽  
Evolutionarily Conserved ◽  
The Right ◽  
And Function ◽  
The 19Th Century ◽  
High Resolution Microscopy

The centriole is a multifunctional structure that organizes centrosomes and cilia and is important for cell signaling, cell cycle progression, polarity, and motility. Defects in centriole number and structure are associated with human diseases including cancer and ciliopathies. Discovery of the centriole dates back to the 19th century. However, recent advances in genetic and biochemical tools, development of high-resolution microscopy, and identification of centriole components have accelerated our understanding of its assembly, function, evolution, and its role in human disease. The centriole is an evolutionarily conserved structure built from highly conserved proteins and is present in all branches of the eukaryotic tree of life. However, centriole number, size, and organization varies among different organisms and even cell types within a single organism, reflecting its cell type–specialized functions. In this review, we provide an overview of our current understanding of centriole biogenesis and how variations around the same theme generate alternatives for centriole formation and function.

scholarly journals A systems perspective of heterocellular signaling

2018 ◽  
Vol 62 (4) ◽  
pp. 607-617 ◽  
Author(s):  
Alan Wells ◽  
H. Steven Wiley
Keyword(s):  
Cell Types ◽  
Regulatory Processes ◽  
Technical Developments ◽  
Building Models ◽  
Realistic Description ◽  
Multiple Cell ◽  
Solid Foundation ◽  
And Function ◽  
Multicellular Organisms ◽  
Different Cell Types

Signal exchange between different cell types is essential for development and function of multicellular organisms, and its dysregulation is causal in many diseases. Unfortunately, most cell-signaling work has employed single cell types grown under conditions unrelated to their native context. Recent technical developments have started to provide the tools needed to follow signaling between multiple cell types, but gaps in the information they provide have limited their usefulness in building realistic models of heterocellular signaling. Currently, only targeted assays have the necessary sensitivity, selectivity, and spatial resolution to usefully probe heterocellular signaling processes, but these are best used to test specific, mechanistic models. Decades of systems biology research with monocultures has provided a solid foundation for building models of heterocellular signaling, but current models lack a realistic description of regulated proteolysis and the feedback processes triggered within and between cells. Identification and understanding of key regulatory processes in the extracellular environment and of recursive signaling patterns between cells will be essential to building predictive models of heterocellular systems.

scholarly journals Capturing large genomic contexts for accurately predicting enhancer-promoter interactions

2021 ◽  
Author(s):  
Ken Chen ◽  
Huiying Zhao ◽  
Yuedong Yang
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Cell Types ◽  
Training Data ◽  
Independent Test ◽  
Distant Target ◽  
Comparable Performance ◽  
Precision Recall Curve ◽  
Different Cell Types ◽  
The Impact

AbstractAccurately identifying enhancer-promoter interactions (EPIs) is challenging because enhancers usually act on the promoters of distant target genes. Although a variety of machine learning and deep learning models have been developed, many of them are not designed to or could not be well applied to predict EPIs in cell types different from the training data. In this study, we develop the TransEPI model for EPI prediction based on datasets derived from Hi-C and ChIA-PET data. TransEPI compiles genomic features from large intervals harboring the enhancer-promoter pair and adopts a Transformer-based architecture to capture the long-range dependencies. Thus, TransEPI could achieve more accurate prediction by addressing the impact of other genomic loci that may competitively interact with the enhancer-promoter pair. We evaluate TransEPI in a challenging scenario, where the independent test samples are predicted by models trained on the data from different cell types and chromosomes. TransEPI robustly predicts cross-cell-type EPI prediction by achieving comparable performance in cross-validation and independent test. More importantly, TransEPI significantly outperforms the state-of-the-art EPI models on the independent test datasets, with the Area Under Precision-Recall Curve (auPRC) score increasing by 48.84 % on average. Hence, TransEPI is applicable for accurate EPI prediction in cell types without chromatin structure data. Moreover, we find the TransEPI framework could also be extended to identify the target gene of non-coding mutations, which may facilitate studying pathogenic non-coding mutations.

scholarly journals Neonatal Fc receptor (FcRn) – not only transporter of maternal IgG

2018 ◽  
Vol 72 ◽  
pp. 701-727
Author(s):  
Joanna E. Mikulska
Keyword(s):  
Mhc Class I ◽  
Current Knowledge ◽  
Cell Types ◽  
Fc Receptor ◽  
Class I ◽  
Neonatal Fc Receptor ◽  
The Status ◽  
And Function ◽  
Different Cell Types ◽  
Maternal Igg

The neonatal Fc receptor, (FcRn) is a transmembrane, heterodimeric glycoprotein with a structure similar to MHC class I molecules. In contrast to MHC class I antigens, FcRn does not bind to peptides (antigens) but interacts with the Fc fragment of IgG and albumin. The FcRn-IgG interaction as well as the FcRn-albumin interaction occur at acidic pH (optimally at pH 5.0-6.5) but not in physiological environment. These two ligands bind to distinct binding sites on the receptor molecule and by different mechanisms. Now, it is known that the expression of FcRn is not restricted to sites involved in the transport of maternal IgG, and this receptor is not responsible only for transfer the passive immunity from mother to the offspring. But FcRn has a much broader range of expression and function, throughout life and in many different cell types and tissues of humans and animals. This review summarizes the status of our knowledge on the expression, interaction with ligands and functions of the neonatal Fc receptor. This article shows also the possibilities of utilizing a current knowledge on FcRn for therapeutic purposes.

scholarly journals Soluble levels of cytosolic tubulin regulate ciliary length control

2011 ◽  
Vol 22 (6) ◽  
pp. 806-816 ◽  
Author(s):  
Neeraj Sharma ◽  
Zachary A. Kosan ◽  
Jannese E. Stallworth ◽  
Nicolas F. Berbari ◽  
Bradley K. Yoder
Keyword(s):  
Primary Cilium ◽  
Cell Types ◽  
Microtubule Network ◽  
Subsequent Increase ◽  
Developmental Defects ◽  
Pharmacological Agents ◽  
Developmental Abnormalities ◽  
Evolutionarily Conserved ◽  
Cytoskeletal Dynamics ◽  
Different Cell Types

The primary cilium is an evolutionarily conserved dynamic organelle important for regulating numerous signaling pathways, and, as such, mutations disrupting ciliogenesis result in a variety of developmental abnormalities and postnatal disorders. The length of the cilium is regulated by the cell through largely unknown mechanisms. Normal cilia length is important, as either shortened or elongated cilia have been associated with disease and developmental defects. Here we explore the importance of cytoskeletal dynamics in regulating cilia length. Using pharmacological approaches in different cell types, we demonstrate that actin depolymerization or stabilization and protein kinase A activation result in a rapid elongation of the primary cilium. The effects of pharmacological agents on cilia length are associated with a subsequent increase in soluble tubulin levels and can be impaired by depletion of soluble tubulin with taxol. In addition, subtle nocodazole treatment was able to induce ciliogenesis under conditions in which cilia are not normally formed and also increases cilia length on cells that have already established cilia. Together these data indicate that cilia length can be regulated through changes in either the actin or microtubule network and implicate a possible role for soluble tubulin levels in cilia length control.

scholarly journals Cargo Recognition and Function of Selective Autophagy Receptors in Plants

2021 ◽  
Vol 22 (3) ◽  
pp. 1013
Author(s):  
Shuwei Luo ◽  
Xifeng Li ◽  
Yan Zhang ◽  
Yunting Fu ◽  
Baofang Fan ◽  
...  
Keyword(s):  
Cellular Response ◽  
Plant Responses ◽  
Biological Functions ◽  
Biotic And Abiotic Stresses ◽  
Selective Autophagy ◽  
Evolutionarily Conserved ◽  
Autophagic Degradation ◽  
Species Specific ◽  
And Function ◽  
Cellular Components

Autophagy is a major quality control system for degradation of unwanted or damaged cytoplasmic components to promote cellular homeostasis. Although non-selective bulk degradation of cytoplasm by autophagy plays a role during cellular response to nutrient deprivation, the broad roles of autophagy are primarily mediated by selective clearance of specifically targeted components. Selective autophagy relies on cargo receptors that recognize targeted components and recruit them to autophagosomes through interaction with lapidated autophagy-related protein 8 (ATG8) family proteins anchored in the membrane of the forming autophagosomes. In mammals and yeast, a large collection of selective autophagy receptors have been identified that mediate the selective autophagic degradation of organelles, aggregation-prone misfolded proteins and other unwanted or nonnative proteins. A substantial number of selective autophagy receptors have also been identified and functionally characterized in plants. Some of the autophagy receptors in plants are evolutionarily conserved with homologs in other types of organisms, while a majority of them are plant-specific or plant species-specific. Plant selective autophagy receptors mediate autophagic degradation of not only misfolded, nonactive and otherwise unwanted cellular components but also regulatory and signaling factors and play critical roles in plant responses to a broad spectrum of biotic and abiotic stresses. In this review, we summarize the research on selective autophagy in plants, with an emphasis on the cargo recognition and the biological functions of plant selective autophagy receptors.

scholarly journals Maternal Overnutrition Programs Central Inflammation and Addiction-Like Behavior in Offspring

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Larisa Montalvo-Martínez ◽  
Roger Maldonado-Ruiz ◽  
Marcela Cárdenas-Tueme ◽  
Diana Reséndez-Pérez ◽  
Alberto Camacho
Keyword(s):  
Gene Expression ◽  
Fetal Programming ◽  
Gene Expression Pattern ◽  
Cell Types ◽  
Addictive Behavior ◽  
Adaptive Responses ◽  
Inflammatory Phenotype ◽  
Pregnancy And Lactation ◽  
Maternal Overnutrition ◽  
The Impact

Obesity or maternal overnutrition during pregnancy and lactation might have long-term consequences in offspring health. Fetal programming is characterized by adaptive responses to specific environmental conditions during early life stages. Programming alters gene expression through epigenetic modifications leading to a transgenerational effect of behavioral phenotypes in the offspring. Maternal intake of hypercaloric diets during fetal development programs aberrant behaviors resembling addiction in offspring. Programming by hypercaloric surplus sets a gene expression pattern modulating axonal pruning, synaptic signaling, and synaptic plasticity in selective regions of the reward system. Likewise, fetal programming can promote an inflammatory phenotype in peripheral and central sites through different cell types such as microglia and T and B cells, which contribute to disrupted energy sensing and behavioral pathways. The molecular mechanism that regulates the central and peripheral immune cross-talk during fetal programming and its relevance on offspring’s addictive behavior susceptibility is still unclear. Here, we review the most relevant scientific reports about the impact of hypercaloric nutritional fetal programming on central and peripheral inflammation and its effects on addictive behavior of the offspring.

scholarly journals Emerging roles of the bone morphogenetic protein pathway in cancer: potential therapeutic target for kinase inhibition

2016 ◽  
Vol 44 (4) ◽  
pp. 1117-1134 ◽  
Author(s):  
Pawina Jiramongkolchai ◽  
Philip Owens ◽  
Charles C. Hong
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Therapeutic Target ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Bone Morphogenetic Protein Pathway ◽  
Bmp Signalling ◽  
Unique Cell ◽  
The Impact

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-β (TGF-β) family signalling pathway. Similar to TGF-β, the complex roles of BMPs in development and disease are demonstrated by their dichotomous roles in various cancers and cancer stages. Although early studies implicated BMP signalling in tumour suppressive phenotypes, the results of more recent experiments recognize BMPs as potent tumour promoters. Many of these complexities are becoming illuminated by understanding the role of BMPs in their contextual role in unique cell types of cancer and the impact of their surrounding tumour microenvironment. Here we review the emerging roles of BMP signalling in cancer, with a focus on the molecular underpinnings of BMP signalling in individual cancers as a valid therapeutic target for cancer prevention and treatment.

scholarly journals Understanding the Relevance of DNA Methylation Changes in Immune Differentiation and Disease

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 110 ◽  
Author(s):  
Carlos de la Calle-Fabregat ◽  
Octavio Morante-Palacios ◽  
Esteban Ballestar
Keyword(s):  
Dna Methylation ◽  
Cell Types ◽  
Epigenetic Modifications ◽  
Human Organism ◽  
Cell Phenotype ◽  
Effector Cells ◽  
Technological Advances ◽  
And Function ◽  
Different Cell Types ◽  
External Stimuli

Immune cells are one of the most complex and diverse systems in the human organism. Such diversity implies an intricate network of different cell types and interactions that are dependently interconnected. The processes by which different cell types differentiate from progenitors, mature, and finally exert their function requires an orchestrated succession of molecular processes that determine cell phenotype and function. The acquisition of these phenotypes is highly dependent on the establishment of unique epigenetic profiles that confer identity and function on the various types of effector cells. These epigenetic mechanisms integrate microenvironmental cues into the genome to establish specific transcriptional programs. Epigenetic modifications bridge environment and genome regulation and play a role in human diseases by their ability to modulate physiological programs through external stimuli. DNA methylation is one of the most ubiquitous, stable, and widely studied epigenetic modifications. Recent technological advances have facilitated the generation of a vast amount of genome-wide DNA methylation data, providing profound insights into the roles of DNA methylation in health and disease. This review considers the relevance of DNA methylation to immune system cellular development and function, as well as the participation of DNA methylation defects in immune-mediated pathologies, illustrated by selected paradigmatic diseases.

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