scholarly journals Differential Kat3 Usage Orchestrates the Integration of Cellular Metabolism with Differentiation

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5884
Author(s):  
Xiaohui Hu ◽  
Masaya Ono ◽  
Nyam-Osor Chimge ◽  
Keisuke Chosa ◽  
Cu Nguyen ◽  
...  
Keyword(s):  
Cell Biology ◽  
Immune Cell ◽  
Wnt Signaling Pathway ◽  
Cellular Metabolism ◽  
Signaling Cascades ◽  
Evolutionarily Conserved ◽  
And Migration ◽  
Nuclear Receptor Family ◽  
And Function ◽  
Multiple Signaling

The integration of cellular status with metabolism is critically important and the coupling of energy production and cellular function is highly evolutionarily conserved. This has been demonstrated in stem cell biology, organismal, cellular and tissue differentiation and in immune cell biology. However, a molecular mechanism delineating how cells coordinate and couple metabolism with transcription as they navigate quiescence, growth, proliferation, differentiation and migration remains in its infancy. The extreme N-termini of the Kat3 coactivator family members, CBP and p300, by far the least homologous regions with only 66% identity, interact with members of the nuclear receptor family, interferon activated Stat1 and transcriptionally competent β-catenin, a critical component of the Wnt signaling pathway. We now wish to report based on multiomic and functional investigations, utilizing p300 knockdown, N-terminal p300 edited and p300 S89A edited cell lines and p300 S89A knockin mice, that the N-termini of the Kat3 coactivators provide a highly evolutionarily conserved hub to integrate multiple signaling cascades to coordinate cellular metabolism with the regulation of cellular status and function.

scholarly journals Nonneuronal Cholinergic System in Breast Tumors and Dendritic Cells: Does It Improve or Worsen the Response to Tumor?

2013 ◽  
Vol 2013 ◽  
pp. 1-12
Author(s):  
Marisa Vulcano ◽  
María Gabriela Lombardi ◽  
María Elena Sales
Keyword(s):  
Dendritic Cells ◽  
Cholinergic System ◽  
Parasympathetic Nervous System ◽  
Immune Cell ◽  
Breast Tumors ◽  
Cell Types ◽  
Cellular Functions ◽  
And Migration ◽  
And Function

Besides being the main neurotransmitter in the parasympathetic nervous system, acetylcholine (ACh) can act as a signaling molecule in nonneuronal tissues. For this reason, ACh and the enzymes that synthesize and degrade it (choline acetyltransferase and acetylcholinesterase) as well as muscarinic (mAChRs) and nicotinic receptors conform the non-neuronal cholinergic system (nNCS). It has been reported that nNCS regulates basal cellular functions including survival, proliferation, adhesion, and migration. Moreover, nNCS is broadly expressed in tumors and in different components of the immune system. In this review, we summarize the role of nNCS in tumors and in different immune cell types focusing on the expression and function of mAChRs in breast tumors and dendritic cells (DCs) and discussing the role of DCs in breast cancer.

scholarly journals The Fox Genes in the Liver: From Organogenesis to Functional Integration

2010 ◽  
Vol 90 (1) ◽  
pp. 1-22 ◽  
Author(s):  
John Le lay ◽  
Klaus H. Kaestner
Keyword(s):  
Dna Binding ◽  
Regulatory Networks ◽  
Functional Integration ◽  
Binding Motif ◽  
Transcriptional Regulatory Networks ◽  
Transcriptional Regulatory ◽  
Evolutionarily Conserved ◽  
Dna Binding Factors ◽  
And Function ◽  
Multiple Signaling

Formation and function of the liver are highly controlled, essential processes. Multiple signaling pathways and transcriptional regulatory networks cooperate in this complex system. The evolutionarily conserved FOX, for Forkhead bOX, class of transcriptional regulators is critical to many aspects of liver development and function. The FOX proteins are small, mostly monomeric DNA binding factors containing the so-called winged helix DNA binding motif that distinguishes them from other classes of transcription factors. We discuss the biochemical and genetic roles of Foxa, Foxl1, Foxm1, and Foxo, as these have been shown to regulate many processes throughout the life of the organ, controlling both formation and function of the liver.

Biology of the Heparanase–Heparan Sulfate Axis and Its Role in Disease Pathogenesis

2021 ◽  
Vol 47 (03) ◽  
pp. 240-253 ◽  
Author(s):  
Israel Vlodavsky ◽  
Uri Barash ◽  
Hien M. Nguyen ◽  
Shi-Ming Yang ◽  
Neta Ilan
Keyword(s):  
Cell Proliferation ◽  
Heparan Sulfate ◽  
Cell Activation ◽  
Immune Cell ◽  
Enzyme Activation ◽  
Cell Of Origin ◽  
Immune Cell Activation ◽  
Cytokines And Chemokines ◽  
And Function ◽  
Multiple Signaling

AbstractCell surface proteoglycans are important constituents of the glycocalyx and participate in cell–cell and cell–extracellular matrix (ECM) interactions, enzyme activation and inhibition, and multiple signaling routes, thereby regulating cell proliferation, survival, adhesion, migration, and differentiation. Heparanase, the sole mammalian heparan sulfate degrading endoglycosidase, acts as an “activator” of HS proteoglycans, thus regulating tissue hemostasis. Heparanase is a multifaceted enzyme that together with heparan sulfate, primarily syndecan-1, drives signal transduction, immune cell activation, exosome formation, autophagy, and gene transcription via enzymatic and nonenzymatic activities. An important feature is the ability of heparanase to stimulate syndecan-1 shedding, thereby impacting cell behavior both locally and distally from its cell of origin. Heparanase releases a myriad of HS-bound growth factors, cytokines, and chemokines that are sequestered by heparan sulfate in the glycocalyx and ECM. Collectively, the heparan sulfate–heparanase axis plays pivotal roles in creating a permissive environment for cell proliferation, differentiation, and function, often resulting in the pathogenesis of diseases such as cancer, inflammation, endotheliitis, kidney dysfunction, tissue fibrosis, and viral infection.

scholarly journals ROS signaling cascades: dual regulations for osteoclast and osteoblast

2020 ◽  
Vol 52 (10) ◽  
pp. 1055-1062 ◽  
Author(s):  
Huaqiang Tao ◽  
Gaoran Ge ◽  
Xiaolong Liang ◽  
Weicheng Zhang ◽  
Houyi Sun ◽  
...  
Keyword(s):  
Cell Biology ◽  
Osteoblast Differentiation ◽  
Cell Metabolism ◽  
Bone Cell ◽  
Bone Diseases ◽  
Signaling Cascades ◽  
Bone Homeostasis ◽  
Ros Signaling ◽  
Osteoblast Activity ◽  
And Function

Abstract Accumulating evidence indicates that intracellular reactive oxygen species (ROS) production is highly involved in bone homeostasis by intervening osteoclast or osteoblast differentiation. Interestingly, ROS that are known as oxidizing agents exert dose-dependent biphasic properties in bone remodeling, including preventing osteoblast activity but accelerating osteoclast resorption. ROS mainly composed of superoxide anion radical, hydroxyl radical, nitric oxide, and two-electron reduction product hydrogen peroxide, which are important components to regulate bone cell metabolism and function in mammal skeleton. These free radicals can be partly produced in bone and boosted in an inflammation state. Although numerous researches have emphasized the impacts of ROS on bone cell biology and verified the mechanism of ROS signaling cascades, the recapitulatory commentary is necessary. In this review article, we particularly focus on the regulation of the intracellular ROS and its potential mechanism impacting on cell-signaling transduction in osteoclast and osteoblast differentiation for preferable understanding the pathogenesis and searching for novel therapeutic protocols for human bone diseases.

scholarly journals Pan-cancer analysis combined with experiments predicts CTHRC1 as a therapeutic target for human cancers

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dazhao Peng ◽  
Cheng Wei ◽  
Xiaoyang Zhang ◽  
Shenghui Li ◽  
Hao Liang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Therapeutic Target ◽  
Immune Cell ◽  
Single Gene ◽  
Wnt Signaling Pathway ◽  
Disease Process ◽  
Genetic Alterations ◽  
Human Cancers ◽  
And Function ◽  
Pan Cancer

Abstract Background The function of collagen triple helix repeat containing 1 (CTHRC1) as an oncogene has been reported in a growing number of publications. Bioinformatics methods represent a beneficial approach to examine the mechanism and function of the CTHRC1 gene in the disease process of cancers from a pan-cancer perspective. Methods In this study, using the online databases UCSC, NCBI, HPA, TIMER2, Oncomine, GEPIA, UALCAN, cBioPortal, COSMIC, MEXPRESS, STRING, CCLE, LinkedOmics, GTEx, TCGA, CGGA, and SangerBox, we focused on the relationship between CTHRC1 and tumorigenesis, progression, methylation, immunity, and prognosis. qPCR was used to detect CTHRC1 expression in glioma tissues and cell lines. Results The pan-cancer analysis showed that CTHRC1 was overexpressed in most tumors, and a significant correlation was observed between CTHRC1 expression and the prognosis of patients with cancer. CTHRC1 genetic alterations occur in diverse tumors and are associated with tumor progression. Levels of CTHRC1 promoter methylation were decreased in most cancer tissues compared with normal tissues. In addition, CTHRC1 coordinated the activity of ICP genes through diverse signal transduction pathways, was also associated with immune cell infiltration and the tumor microenvironment, and potentially represented a promising immunotherapy target. We identified CTHRC1-related genes across cancers using the GEPIA2 tool. The single-gene GO analysis of CTHRC1 across cancers showed that it was involved in some signaling pathways and biological processes, such as the Wnt signaling pathway, cell migration, and positive regulation of protein binding. The expression and function of CTHRC1 were also further verified in glioma tissues and cell lines. Conclusions CTHRC1 is overexpressed in various cancer types and functions as an important oncogene that may promote tumorigenesis and development through different mechanisms. CTHRC1 may represent an important therapeutic target for human cancers.

Cell Morphology and Migration of Nucleus Pulposus Cells Depends on Substrate Stiffness and Ligand

2012 ◽  
Author(s):  
Priscilla Y. Hwang ◽  
Christopher L. Gilchrist ◽  
Aubrey T. Francisco ◽  
Jun Chen ◽  
Lori A. Setton
Keyword(s):  
Nucleus Pulposus ◽  
Cell Biology ◽  
Imaging Techniques ◽  
Matrix Proteins ◽  
Cell Phenotype ◽  
Nucleus Pulposus Cells ◽  
Cell Clustering ◽  
And Migration ◽  
And Function

Changes in nucleus pulposus (NP) cell phenotype and morphology are implicated in the progression of intervertebral disc (IVD) disorders. Understanding how changes in the NP cell microenvironment influence cell behavior and function is important for revealing how pathology-related changes in IVD extracellular matrix may affect NP cell biology. In this study, live-cell imaging techniques were utilized to study changes in cell migration and morphology when cultured upon substrates of different matrix proteins and stiffnesses. Results indicate that soft substrates containing matrix proteins promote cell clustering and cell-cell interactions which mimic in vivo conditions of healthy NP cells.

scholarly journals Prox1 Induces Lymphatic Endothelial Differentiation via Integrin α9 and Other Signaling Cascades

2007 ◽  
Vol 18 (4) ◽  
pp. 1421-1429 ◽  
Author(s):  
Koichi Mishima ◽  
Tetsuro Watabe ◽  
Akira Saito ◽  
Yasuhiro Yoshimatsu ◽  
Natsuko Imaizumi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Cascades ◽  
Vegf Receptor ◽  
Lymphatic Endothelial Cells ◽  
Cellular Behavior ◽  
Prox1 Expression ◽  
Homeobox Transcription Factor ◽  
Lymphatic Development ◽  
And Migration ◽  
Multiple Signaling

During embryonic lymphatic development, a homeobox transcription factor Prox1 plays important roles in sprouting and migration of a subpopulation of blood vessel endothelial cells (BECs) toward VEGF-C–expressing cells. However, effects of Prox1 on endothelial cellular behavior remain to be elucidated. Here, we show that Prox1, via induction of integrin α9 expression, inhibits sheet formation and stimulates motility of endothelial cells. Prox1-expressing BECs preferentially migrated toward VEGF-C via up-regulation of the expression of integrin α9 and VEGF receptor 3 (VEGFR3). In mouse embryos, expression of VEGFR3 and integrin α9 is increased in Prox1-expressing lymphatic endothelial cells (LECs) compared with BECs. Knockdown of Prox1 expression in human LECs led to decrease in the expression of integrin α9 and VEGFR3, resulting in the decreased chemotaxes toward VEGF-C. These findings suggest that Prox1 plays important roles in conferring and maintaining the characteristics of LECs by modulating multiple signaling cascades and that integrin α9 may function as a key regulator of lymphangiogenesis acting downstream of Prox1.

The macrophage odorant receptor Olfr78 mediates the lactate-induced M2 phenotype of tumor-associated macrophages

2021 ◽  
Vol 118 (37) ◽  
pp. e2102434118
Author(s):  
Sri Murugan Poongkavithai Vadevoo ◽  
Gowri Rangaswamy Gunassekaran ◽  
ChaeEun Lee ◽  
NaHye Lee ◽  
Jiyoun Lee ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Immune Cell ◽  
Odorant Receptor ◽  
Odorant Receptors ◽  
Tumor Associated Macrophages ◽  
Immune Cell Population ◽  
Lactate Sensor ◽  
And Function ◽  
Multiple Signaling ◽  
G Protein Coupled

Expression and function of odorant receptors (ORs), which account for more than 50% of G protein–coupled receptors, are being increasingly reported in nonolfactory sites. However, ORs that can be targeted by drugs to treat diseases remain poorly identified. Tumor-derived lactate plays a crucial role in multiple signaling pathways leading to generation of tumor-associated macrophages (TAMs). In this study, we hypothesized that the macrophage OR Olfr78 functions as a lactate sensor and shapes the macrophage–tumor axis. Using Olfr78+/+ and Olfr78−/− bone marrow–derived macrophages with or without exogenous Olfr78 expression, we demonstrated that Olfr78 sensed tumor-derived lactate, which was the main factor in tumor-conditioned media responsible for generation of protumoral M2-TAMs. Olfr78 functioned together with Gpr132 to mediate lactate-induced generation of protumoral M2-TAMs. In addition, syngeneic Olfr78-deficient mice exhibited reduced tumor progression and metastasis together with an increased anti- versus protumoral immune cell population. We propose that the Olfr78–lactate interaction is a therapeutic target to reduce and prevent tumor progression and metastasis.

scholarly journals Extracellular Matrix Enzymes and Immune Cell Biology

2021 ◽  
Vol 8 ◽  
Author(s):  
Meagan McMahon ◽  
Siying Ye ◽  
Jess Pedrina ◽  
Daniel Dlugolenski ◽  
John Stambas
Keyword(s):  
Extracellular Matrix ◽  
Cell Biology ◽  
Cell Function ◽  
Immune Cell ◽  
Vital Role ◽  
Immune Cell Function ◽  
Immune Cell Migration ◽  
And Function ◽  
A Current

Remodelling of the extracellular matrix (ECM) by ECM metalloproteinases is increasingly being associated with regulation of immune cell function. ECM metalloproteinases, including Matrix Metalloproteinases (MMPs), A Disintegrin and Metalloproteinases (ADAMs) and ADAMs with Thombospondin-1 motifs (ADAMTS) play a vital role in pathogen defence and have been shown to influence migration of immune cells. This review provides a current summary of the role of ECM enzymes in immune cell migration and function and discusses opportunities and limitations for development of diagnostic and therapeutic strategies targeting metalloproteinase expression and activity in the context of infectious disease.

scholarly journals Wnt signalling and the control of cellular metabolism

2010 ◽  
Vol 427 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Jaswinder K. Sethi ◽  
Antonio Vidal-Puig
Keyword(s):  
Cell Proliferation ◽  
Cell Biology ◽  
Cellular Metabolism ◽  
Cellular Level ◽  
Wnt Signalling ◽  
Tissue Remodelling ◽  
Experimental Systems ◽  
Signalling Network ◽  
Tightly Coupled ◽  
And Function

At the cellular level, the biological processes of cell proliferation, growth arrest, differentiation and apoptosis are all tightly coupled to appropriate alterations in metabolic status. In the case of cell proliferation, this requires redirecting metabolic pathways to provide the fuel and basic components for new cells. Ultimately, the successful co-ordination of cell-specific biology with cellular metabolism underscores multicellular processes as diverse as embryonic development, adult tissue remodelling and cancer cell biology. The Wnt signalling network has been implicated in all of these areas. While each of the Wnt-dependent signalling pathways are being individually delineated in a range of experimental systems, our understanding of how they integrate and regulate cellular metabolism is still in its infancy. In the present review we reassess the roles of Wnt signalling in functionally linking cellular metabolism to tissue development and function.

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