scholarly journals Molecular Mechanisms of Heat Shock Factors in Cancer

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1202
Author(s):  
Mikael Christer Puustinen ◽  
Lea Sistonen
Keyword(s):  
Heat Shock ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Heat Shock Factors ◽  
Therapeutic Approaches ◽  
The Past ◽  
Cancer Types ◽  
Cellular Pathways ◽  
As Stress ◽  
Regulatory Functions

Malignant transformation is accompanied by alterations in the key cellular pathways that regulate development, metabolism, proliferation and motility as well as stress resilience. The members of the transcription factor family, called heat shock factors (HSFs), have been shown to play important roles in all of these biological processes, and in the past decade it has become evident that their activities are rewired during tumorigenesis. This review focuses on the expression patterns and functions of HSF1, HSF2, and HSF4 in specific cancer types, highlighting the mechanisms by which the regulatory functions of these transcription factors are modulated. Recently developed therapeutic approaches that target HSFs are also discussed.

scholarly journals HSFs drive stress type-specific transcription of genes and enhancers

2021 ◽  
Author(s):  
Samu V Himanen ◽  
Mikael C Puustinen ◽  
Alejandro J Da Silva ◽  
Anniina Vihervaara ◽  
Lea Sistonen
Keyword(s):  
Oxidative Stress ◽  
Heat Shock ◽  
Rna Polymerase Ii ◽  
Molecular Mechanisms ◽  
Gene Promoters ◽  
Heat Shock Factors ◽  
Pol Ii ◽  
Bona Fide ◽  
Stressed Cells ◽  
First Time

Reprogramming of transcription is critical for the survival under cellular stress. Heat shock has provided an excellent model to investigate nascent transcription in stressed cells, but the molecular mechanisms orchestrating RNA synthesis during other types of stress are unknown. We utilized PRO-seq and ChIP-seq to study how Heat Shock Factors, HSF1 and HSF2, coordinate transcription at genes and enhancers upon oxidative stress and heat shock. We show that pause-release of RNA polymerase II (Pol II) is a universal mechanism regulating gene transcription in stressed cells, while enhancers are activated at the level of Pol II recruitment. Moreover, besides functioning as conventional promoter-binding transcription factors, HSF1 and HSF2 bind to stress-induced enhancers to trigger Pol II pause-release from poised gene promoters. Importantly, HSFs act at distinct genes and enhancers in a stress type-specific manner. HSF1 binds to many chaperone genes upon oxidative and heat stress but activates them only in heat-shocked cells. Under oxidative stress, HSF1 and HSF2 trans-activate genes independently of each other, demonstrating, for the first time, that HSF2 is a bona fide transcription factor. Taken together, we show that HSFs function as multi-stress-responsive factors that activate specific genes and enhancers when encountering changes in temperature and redox state.

Targeting Mutant KRAS for Anticancer Therapy

2019 ◽  
Vol 19 (23) ◽  
pp. 2098-2113 ◽  
Author(s):  
Fengqian Chen ◽  
Martin P. Alphonse ◽  
Yan Liu ◽  
Qi Liu
Keyword(s):  
Future Development ◽  
Anticancer Therapy ◽  
Therapeutic Strategies ◽  
Therapeutic Approaches ◽  
Cellular Processes ◽  
The Past ◽  
Cancer Types

: Over the past decades, designing therapeutic strategies to target KRAS-mutant cancers, which is one of the most frequent mutant oncogenes among all cancer types, have proven unsuccessful regardless of many concerted attempts. There are key challenges for KRAS-mutant anticancer therapy, as the complex cellular processes involved in KRAS signaling has present. Herein, we highlight the emerging therapeutic approaches for inhibiting KRAS signaling and blocking KRAS functions, in hope to serve as a more effective guideline for future development of therapeutics.

scholarly journals Dual Effects of Non-Coding RNAs (ncRNAs) in Cancer Stem Cell Biology

2020 ◽  
Vol 21 (18) ◽  
pp. 6658 ◽  
Author(s):  
Athina A. Kyriazi ◽  
Efstathios Papiris ◽  
Konstantinos Kitsos Kalyvianakis ◽  
George Sakellaris ◽  
Stavroula Baritaki
Keyword(s):  
Cell Biology ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Circular Rnas ◽  
Stem Cell Biology ◽  
Disease Treatment ◽  
The Past ◽  
Therapeutic Value ◽  
Non Coding Rnas ◽  
Regulatory Functions

The identification of cancer stem cells (CSCs) as initiators of carcinogenesis has revolutionized the era of cancer research and our perception for the disease treatment options. Additional CSC features, including self-renewal and migratory and invasive capabilities, have further justified these cells as putative diagnostic, prognostic, and therapeutic targets. Given the CSC plasticity, the identification of CSC-related biomarkers has been a serious burden in CSC characterization and therapeutic targeting. Over the past decades, a compelling amount of evidence has demonstrated critical regulatory functions of non-coding RNAs (ncRNAs) on the exclusive features of CSCs. We now know that ncRNAs may interfere with signaling pathways, vital for CSC phenotype maintenance, such as Notch, Wnt, and Hedgehog. Here, we discuss the multifaceted contribution of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as representative ncRNA classes, in sustaining the CSC-like traits, as well as the underlying molecular mechanisms of their action in various CSC types. We further discuss the use of CSC-related ncRNAs as putative biomarkers of high diagnostic, prognostic, and therapeutic value.

scholarly journals Emerging Genetic Tools to Investigate Molecular Pathways Related to Heat Stress in Chickens: A Review

Animals ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 46
Author(s):  
Francesco Perini ◽  
Filippo Cendron ◽  
Giacomo Rovelli ◽  
Cesare Castellini ◽  
Martino Cassandro ◽  
...  
Keyword(s):  
Heat Stress ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Chicken Meat ◽  
Molecular Pathways ◽  
Heat Shock Factors ◽  
Genetic Tools ◽  
The Past ◽  
Commercial Chicken ◽  
Shock Proteins

Chicken products are the most consumed animal-sourced foods at a global level across greatly diverse cultures, traditions, and religions. The consumption of chicken meat has increased rapidly in the past few decades and chicken meat is the main animal protein source in developing countries. Heat stress is one of the environmental factors which decreases the productive performance of poultry and meat quality. Heat stress produces the over-expression of heat shock factors and heat shock proteins in chicken tissues. Heat shock proteins regulate several molecular pathways in cells in response to stress conditions, changing the homeostasis of cells and tissues. These changes can affect the physiology of the tissue and hence the production ability of chickens. Indeed, commercial chicken strains can reach a high production level, but their body metabolism, being comparatively accelerated, has poor thermoregulation. In contrast, native backyard chickens are more adapted to the environments in which they live, with a robustness that allows them to survive and reproduce constantly. In the past few years, new molecular tools have been developed, such as RNA-Seq, Single Nucleotide Polymorphisms (SNPs), and bioinformatics approaches such as Genome-Wide Association Study (GWAS). Based on these genetic tools, many studies have detected the main pathways involved in cellular response mechanisms. In this context, it is necessary to clarify all the genetic and molecular mechanisms involved in heat stress response. Hence, this paper aims to review the ability of the new generation of genetic tools to clarify the molecular pathways associated with heat stress in chickens, offering new perspectives for the use of these findings in the animal breeding field.

scholarly journals Enigma of Retrotransposon Biology in Mammalian Early Embryos and Embryonic Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Ying Yin ◽  
Liquan Zhou ◽  
Shuiqiao Yuan
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Alternative Promoters ◽  
Human Escs ◽  
Early Embryos ◽  
Regulatory Functions

Retrotransposons comprise a significant fraction of mammalian genome with unclear functions. Increasing evidence shows that they are not just remnants of ancient retroviruses but play important roles in multiple biological processes. Retrotransposons are epigenetically silenced in most somatic tissues and become reactivated in early embryos. Notably, abundant retrotransposon expression in mouse embryonic stem cells (ESCs) marks transient totipotency status, while retrotransposon enrichment in human ESCs indicates naive-like status. Some retrotransposon elements retained the capacity to retrotranspose, such as LINE1, producing genetic diversity or disease. Some other retrotransposons reside in the vicinity of endogenous genes and are capable of regulating nearby genes and cell fate, possibly through providing alternative promoters, regulatory modules, or orchestrating high-order chromatin assembly. In addition, retrotransposons may mediate epigenetic memory, regulate gene expression posttranscriptionally, defend virus infection, and so on. In this review, we summarize expression patterns and regulatory functions of different retrotransposons in early embryos and ESCs, as well as document molecular mechanisms controlling retrotransposon expression and their potential functions. Further investigations on the regulatory network of retrotransposons in early embryogenesis and ESCs will provide valuable insights and a deeper understanding of retrotransposon biology. Additionally, endeavors made to unveil the roles of these mysterious elements may facilitate stem cell status conversion and manipulation of pluripotency.

scholarly journals Pharmacological Findings on the Biochemical Bases of Memory Processes: A General View

2004 ◽  
Vol 11 (3-4) ◽  
pp. 159-189 ◽  
Author(s):  
Iván Izquierdo ◽  
Martín Cammarota ◽  
Jorge H. Medina ◽  
Lia R. M. Bevilaqua
Keyword(s):  
Mental Disorders ◽  
Molecular Mechanisms ◽  
Brain Structures ◽  
Fear Memory ◽  
Brain Regions ◽  
General View ◽  
Therapeutic Approaches ◽  
The Past ◽  
New Therapeutic Approaches ◽  
Pharmacological Studies

We have advanced considerably in the past 2 to 3 years in understanding the molecular mechanisms of consolidation, retrieval, and extinction of memories, particularly of fear memory. This advance was mainly due to pharmacological studies in many laboratories using localized brain injections of molecularly specific substances. One area in which significant advances have been made is in understanding that many different brain structures are involved in different memories, and that often several brain regions are involved in processing the same memory. These regions can cooperate or compete with each other, depending on circumstances that are beginning to be identified quite clearly. Another aspect in which major advances were made was retrieval and post-retrieval events, especially extinction, pointing to new therapeutic approaches to fearmotivated mental disorders.

scholarly journals New Insights into Evolution of Plant Heat Shock Factors (Hsfs) and Expression Analysis of Tea Genes in Response to Abiotic Stresses

Plants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 311
Author(s):  
Ping Xu ◽  
Qinwei Guo ◽  
Xin Pang ◽  
Peng Zhang ◽  
Dejuan Kong ◽  
...  
Keyword(s):  
Heat Stress ◽  
Heat Shock ◽  
Plant Species ◽  
Abiotic Stresses ◽  
Developmental Stages ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Heat Shock Factors ◽  
Camellia Species ◽  
Species Specific

Heat shock transcription factor (Hsf) is one of key regulators in plant abotic stress response. Although the Hsf gene family has been identified from several plant species, original and evolution relationship have been fragmented. In addition, tea, an important crop, genome sequences have been completed and function of the Hsf family genes in response to abiotic stresses was not illuminated. In this study, a total of 4208 Hsf proteins were identified within 163 plant species from green algae (Gonium pectorale) to angiosperm (monocots and dicots), which were distributed unevenly into each of plant species tested. The result indicated that Hsf originated during the early evolutionary history of chlorophytae algae and genome-wide genetic varies had occurred during the course of evolution in plant species. Phylogenetic classification of Hsf genes from the representative nine plant species into ten subfamilies, each of which contained members from different plant species, imply that gene duplication had occurred during the course of evolution. In addition, based on RNA-seq data, the member of the Hsfs showed different expression levels in the different organs and at the different developmental stages in tea. Expression patterns also showed clear differences among Camellia species, indicating that regulation of Hsf genes expression varied between organs in a species-specific manner. Furthermore, expression of most Hsfs in response to drought, cold and salt stresses, imply a possible positive regulatory role under abiotic stresses. Expression profiles of nineteen Hsf genes in response to heat stress were also analyzed by quantitative real-time RT-PCR. Several stress-responsive Hsf genes were highly regulated by heat stress treatment. In conclusion, these results lay a solid foundation for us to elucidate the evolutionary origin of plant Hsfs and Hsf functions in tea response to abiotic stresses in the future.

scholarly journals Normal and malignant megakaryopoiesis

2011 ◽  
Vol 13 ◽  
Author(s):  
Qiang Wen ◽  
Benjamin Goldenson ◽  
John D. Crispino
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Molecular Mechanisms ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Therapeutic Approaches ◽  
Unique Form ◽  
The Past ◽  
Development And Differentiation ◽  
Novel Therapeutic

Megakaryopoiesis is the process by which bone marrow progenitor cells develop into mature megakaryocytes (MKs), which in turn produce platelets required for normal haemostasis. Over the past decade, molecular mechanisms that contribute to MK development and differentiation have begun to be elucidated. In this review, we provide an overview of megakaryopoiesis and summarise the latest developments in this field. Specially, we focus on polyploidisation, a unique form of the cell cycle that allows MKs to increase their DNA content, and the genes that regulate this process. In addition, because MKs have an important role in the pathogenesis of acute megakaryocytic leukaemia and a subset of myeloproliferative neoplasms, including essential thrombocythemia and primary myelofibrosis, we discuss the biology and genetics of these disorders. We anticipate that an increased understanding of normal MK differentiation will provide new insights into novel therapeutic approaches that will directly benefit patients.

scholarly journals Multi-Approach Bioinformatics Analysis of Curated Omics Data Provides a Gene Expression Panorama for Multiple Cancer Types

2020 ◽  
Vol 11 ◽  
Author(s):  
Bruno César Feltes ◽  
Joice de Faria Poloni ◽  
Itamar José Guimarães Nunes ◽  
Sara Socorro Faria ◽  
Marcio Dorn
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Gene Expression Omnibus ◽  
Rna Seq ◽  
Multiple Cancer ◽  
Heterogeneous Nature ◽  
Cancer Types ◽  
Learning Analysis ◽  
Overall Survival Analysis

Studies describing the expression patterns and biomarkers for the tumoral process increase in number every year. The availability of new datasets, although essential, also creates a confusing landscape where common or critical mechanisms are obscured amidst the divergent and heterogeneous nature of such results. In this work, we manually curated the Gene Expression Omnibus using rigorous filtering criteria to select the most homogeneous and highest quality microarray and RNA-seq datasets from multiple types of cancer. By applying systems biology approaches, combined with machine learning analysis, we investigated possible frequently deregulated molecular mechanisms underlying the tumoral process. Our multi-approach analysis of 99 curated datasets, composed of 5,406 samples, revealed 47 differentially expressed genes in all analyzed cancer types, which were all in agreement with the validation using TCGA data. Results suggest that the tumoral process is more related to the overexpression of core deregulated machinery than the underexpression of a given gene set. Additionally, we identified gene expression similarities between different cancer types not described before and performed an overall survival analysis using 20 cancer types. Finally, we were able to suggest a core regulatory mechanism that could be frequently deregulated.

Novel Findings of Anti-cancer Property of Propofol

2018 ◽  
Vol 18 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Jiaqiang Wang ◽  
Chien-shan Cheng ◽  
Yan Lu ◽  
Xiaowei Ding ◽  
Minmin Zhu ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Intravenous Anesthetic ◽  
The Past ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Recent Attention

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.

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