scholarly journals WNT Signaling in Disease

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 826 ◽  
Author(s):  
Li Ng ◽  
Prameet Kaur ◽  
Nawat Bunnag ◽  
Jahnavi Suresh ◽  
Isabelle Sung ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Human Disease ◽  
Wnt Pathway ◽  
Adult Life ◽  
Biological Processes ◽  
Vast Array ◽  
Wide Range ◽  
Developmental Signaling

Developmental signaling pathways control a vast array of biological processes during embryogenesis and in adult life. The WNT pathway was discovered simultaneously in cancer and development. Recent advances have expanded the role of WNT to a wide range of pathologies in humans. Here, we discuss the WNT pathway and its role in human disease and some of the advances in WNT-related treatments.

scholarly journals WNT Signaling in Melanoma

2020 ◽  
Vol 21 (14) ◽  
pp. 4852 ◽  
Author(s):  
Anna Gajos-Michniewicz ◽  
Malgorzata Czyz
Keyword(s):  
Wnt Signaling ◽  
Planar Cell Polarity ◽  
Wnt Signaling Pathway ◽  
Adult Life ◽  
Canonical Pathway ◽  
Current View ◽  
Directional Growth ◽  
Wide Range ◽  
Wnt Ligands

WNT-signaling controls important cellular processes throughout embryonic development and adult life, so any deregulation of this signaling can result in a wide range of pathologies, including cancer. WNT-signaling is classified into two categories: β-catenin-dependent signaling (canonical pathway) and β-catenin-independent signaling (non-canonical pathway), the latter can be further divided into WNT/planar cell polarity (PCP) and calcium pathways. WNT ligands are considered as unique directional growth factors that contribute to both cell proliferation and polarity. Origin of cancer can be diverse and therefore tissue-specific differences can be found in WNT-signaling between cancers, including specific mutations contributing to cancer development. This review focuses on the role of the WNT-signaling pathway in melanoma. The current view on the role of WNT-signaling in cancer immunity as well as a short summary of WNT pathway-related drugs under investigation are also provided.

scholarly journals Crosstalk between Fat Mass and Obesity-related (FTO) and multiple WNT signaling pathways

2021 ◽  
Author(s):  
Hyunjoon Kim ◽  
Soohyun Jang ◽  
Young-suk Lee
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Fat Mass ◽  
Wide Spectrum ◽  
Rna Regulation ◽  
Public Data ◽  
Wide Range ◽  
Cell Type Specific ◽  
Canonical Wnt

Fat Mass and Obesity-related (FTO) gene is associated with a diverse set of human diseases. Yet, the functional landscape of FTO remains largely unknown, most likely owing to its wide range of mechanistic roles and cell-type-specific targets. Here, we discover the intricate role of FTO in multiple WNT signaling pathways. Re-analyses of public data identified the bifurcation of canonical and noncanonical WNT pathways as the major role of FTO. In FTO-depleted cells, we find that the canonical WNT/β-Catenin signaling is inhibited in a non-cell autonomous manner via the upregulation of DKK1. Simultaneously, this upregulation of DKK1 promotes cell migration via activating the noncanonical WNT/PCP pathway. Unexpectedly, we also find that the canonical WNT/STOP signaling induces the accumulation of cytoplasmic FTO proteins. This subsequently leads to the stabilization of mRNAs via RNA demethylation, revealing a previously uncharacterized mode of WNT action in RNA regulation. Altogether, this study places the functional context of FTO at the branching point of multiple WNT signaling pathways which may explain the wide spectrum of FTO functions.

Analysis of signaling pathway activity in desmoid-type fibromatosis (DF) to identify druggable pathways.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23558-e23558
Author(s):  
Anja Van De Stolpe ◽  
Martijn Akse ◽  
Eveline den Biezen-Timmermans ◽  
Jean-Yves Blay ◽  
Nicolas Penel
Keyword(s):  
Signaling Pathways ◽  
Wnt Pathway ◽  
Target Genes ◽  
Soft Tissue Tumors ◽  
Tissue Type ◽  
Pathway Activity ◽  
Cell Tissue ◽  
Pathway Expression ◽  
Wide Range

e23558 Background: DF are locally invasive soft tissue tumors of fibroblast origin, with unpredictable course. CTTNB1 mutations are a hallmark of DF. Molecular-targeted therapies are lacking. Recently developed OncoSignal (www.philips.com/oncosignal) pathway activity tests enable quantitative measurement of activity of clinically relevant oncogenic signal transduction pathways (estrogen, progesterone & androgen receptors; PI3K, MAPK-AP1, TGFβ, Notch, Hedgehog, Wnt pathways), based on computational interpretation of expression levels of direct target genes of the pathway-associated transcription factor. Methods: OncoSignal was used to measure activity of signaling pathways on Affymetrix transcriptome data from sporadic DF (n = 128), generated before in our center (GEO database: GSE58697), and from presumably healthy fibroblasts (n = 63) derived from a number of different tissue types (public dataset GSE63626). Pathway activity was expressed on a normalized scale 0-100 (min and max pathway activity score depend on the cell/tissue type analyzed). Comparisons used Mann Whitney test. Results: Mean Notch (43.2+/-7.2 vs 11.2 +/- 5.2; p < .0001), PI3K (54.6 +/- 10.0 vs 48.1 +/- 6.6, p < .0001) and androgen receptor (AR) pathway activities (32.8 +/- 3.7 vs 21.7 +/- 2.4, p < .0001) were increased in DF compared to fibroblasts. MAPK-AP1 pathway activity was lower in DF (40.8+/-6.0 vs 70.2 +/- 9.5; p < .0001). Mean Wnt (p = 0.7), HH (p = 0.8) pathway activities were not different between DF and fibroblasts, however the range in Wnt pathway activity scores was larger in DF (median score 24.1, range 5.3-41.7) than in normal fibroblasts (median 26.0, range 14.6-33.0). Conclusions: The increased activity of Notch, PI3K pathways in DF is consistent with the mesenchymal nature. We confirm here the key role of AR pathway. The wide range of Wnt pathway expression was larger, suggesting the heterogeneity in TD biology, possibly related to the type of CTTNB1 mutations. Overall, the large inter-patient variation in pathway activities is in line with variety of TD course. We identified signaling pathways which may provide novel options for targeted drug treatment.

scholarly journals The physiological role of Wnt pathway in normal development and cancer

2020 ◽  
Vol 245 (5) ◽  
pp. 411-426
Author(s):  
Xiang Li ◽  
Maria A Ortiz ◽  
Leszek Kotula
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Wnt Pathway ◽  
Normal Development ◽  
Cancer Development ◽  
Developmental Processes ◽  
Different Types

Over the decades, many studies have illustrated the critical roles of Wnt signaling pathways in both developmental processes as well as tumorigenesis. Due to the complexity of Wnt signaling regulation, there are still questions to be addressed about ways cells are able to manipulate different types of Wnt pathways in order to fulfill the requirements for normal or cancer development. In this review, we will describe different types of Wnt signaling pathways and their roles in both normal developmental processes and their role in cancer development and progression. Additionally, we will briefly introduce new strategies currently in clinical trials targeting Wnt signaling pathway components for cancer therapy. Impact statement Wnt pathway does not only play a critical role in mammalian development but has been hijacked by cancer cells and the tumor microenvironment to promote tumor progression and metastasis. Recent evidence supports further interrogation of the Wnt pathway for bench-to-bedside translation into cancer therapy. This review highlights the role of the Wnt pathway in normal development and tumorigenesis, along with an overview of new therapies currently undergoing clinical trials.

scholarly journals Role of Physical Exercise and Nutraceuticals in Modulating Molecular Pathways of Osteoarthritis

2021 ◽  
Vol 22 (11) ◽  
pp. 5722
Author(s):  
Alessandro de Sire ◽  
Nicola Marotta ◽  
Cinzia Marinaro ◽  
Claudio Curci ◽  
Marco Invernizzi ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Synergistic Effects ◽  
Molecular Pathways ◽  
Epigenetic Changes ◽  
Pathological Features ◽  
Oxidative Signaling ◽  
Cartilage Extracellular Matrix ◽  
Wide Range ◽  
Comprehensive Picture

Osteoarthritis (OA) is a painful and disabling disease that affects millions of patients. Its etiology is largely unknown, but it is most likely multifactorial. OA pathogenesis involves the catabolism of the cartilage extracellular matrix and is supported by inflammatory and oxidative signaling pathways and marked epigenetic changes. To delay OA progression, a wide range of exercise programs and naturally derived compounds have been suggested. This literature review aims to analyze the main signaling pathways and the evidence about the synergistic effects of these two interventions to counter OA. The converging nutrigenomic and physiogenomic intervention could slow down and reduce the complex pathological features of OA. This review provides a comprehensive picture of a possible signaling approach for targeting OA molecular pathways, initiation, and progression.

scholarly journals Comparative approaches to the study of physiology: Drosophila as a physiological tool

2013 ◽  
Vol 304 (3) ◽  
pp. R177-R188 ◽  
Author(s):  
Wendi S. Neckameyer ◽  
Kathryn J. Argue
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Pattern Formation ◽  
Signaling Pathways ◽  
Human Disease ◽  
Cognitive Disorders ◽  
Model System ◽  
Critical Questions ◽  
Developmental Signaling ◽  
Shed Light

Numerous studies have detailed the extensive conservation of developmental signaling pathways between the model system, Drosophila melanogaster, and mammalian models, but researchers have also profited from the unique and highly tractable genetic tools available in this system to address critical questions in physiology. In this review, we have described contributions that Drosophila researchers have made to mathematical dynamics of pattern formation, cardiac pathologies, the way in which pain circuits are integrated to elicit responses from sensation, as well as the ways in which gene expression can modulate diverse behaviors and shed light on human cognitive disorders. The broad and diverse array of contributions from Drosophila underscore its translational relevance to modeling human disease.

scholarly journals STAT3, a Hub Protein of Cellular Signaling Pathways, Is Triggered by β-Hexaclorocyclohexane

2018 ◽  
Vol 19 (7) ◽  
pp. 2108 ◽  
Author(s):  
Elisabetta Rubini ◽  
Fabio Altieri ◽  
Silvia Chichiarelli ◽  
Flavia Giamogante ◽  
Stefania Carissimi ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Cellular Signaling ◽  
Environmental Pollutants ◽  
Altered Expression ◽  
Exposed Population ◽  
Wide Range ◽  
Hepg2 Cell Lines

Background: Organochlorine pesticides (OCPs) are widely distributed in the environment and their toxicity is mostly associated with the molecular mechanisms of endocrine disruption. Among OCPs, particular attention was focused on the effects of β-hexaclorocyclohexane (β-HCH), a widely common pollutant. A detailed epidemiological study carried out on exposed population in the “Valle del Sacco” found correlations between the incidence of a wide range of diseases and the occurrence of β-HCH contamination. Taking into account the pleiotropic role of the protein signal transducer and activator of transcription 3 (STAT3), its function as a hub protein in cellular signaling pathways triggered by β-HCH was investigated in different cell lines corresponding to tissues that are especially vulnerable to damage by environmental pollutants. Materials and Methods: Human prostate cancer (LNCaP), human breast cancer (MCF-7 and MDA-MB 468), and human hepatoma (HepG2) cell lines were treated with 10 μM β-HCH in the presence or absence of specific inhibitors for different receptors. All samples were subjected to analysis by immunoblotting and RT-qPCR. Results and Conclusions: The preliminary results allow us to hypothesize the involvement of STAT3, through both its canonical and non-canonical pathways, in response to β-HCH. Moreover, we ascertained the role of STAT3 as a master regulator of energy metabolism via the altered expression and localization of HIF-1α and PKM2, respectively, resulting in a Warburg-like effect.

The role of Galactose in human health and disease

Open Medicine ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. 409-419 ◽  
Author(s):  
Muhammad Manwar Hussain ◽  
Mukhtarul Hassan ◽  
Noor Shaik ◽  
Zeeshan Iqbal
Keyword(s):  
Human Health ◽  
Cellular Signaling ◽  
Biological Processes ◽  
Microbial Adhesion ◽  
Wide Range ◽  
Health And Disease ◽  
Stereochemical Properties ◽  
Specific Sugar

AbstractAccording to the universal biological findings, cellular bodies are covered with an intense coating of glycans. Diversity of glycan chains, linked to lipids and proteins is due to isomeric and conformational modifications of various sugar residues, giving rise to unique carbohydrate structures with a wide range of sequences and anomeric configurations. Proteins and lipids, carrying specific sugar residues (like Galactose) with particular stereochemical properties (sequence, anomery and linkages) are involved in broad spectrums of biological processes, including intercellular and intracellular interactions, microbial adhesion and cellular signaling. By studying the role of specific seterochemical features of galactose (Gal), we have improved our understanding about the normal physiology and diseases in human bodies.

scholarly journals Targeting Wnt signaling in colorectal cancer. A Review in the Theme: Cell Signaling: Proteins, Pathways and Mechanisms

2015 ◽  
Vol 309 (8) ◽  
pp. C511-C521 ◽  
Author(s):  
Laura Novellasdemunt ◽  
Pedro Antas ◽  
Vivian S. W. Li
Keyword(s):  
Wnt Signaling ◽  
Cell Fate ◽  
Wnt Pathway ◽  
High Throughput Sequencing ◽  
Wnt Signaling Pathway ◽  
Negative Regulator ◽  
Cell Fate Decisions ◽  
Stem Cell Maintenance ◽  
Evolutionarily Conserved

The evolutionarily conserved Wnt signaling pathway plays essential roles during embryonic development and tissue homeostasis. Notably, comprehensive genetic studies in Drosophila and mice in the past decades have demonstrated the crucial role of Wnt signaling in intestinal stem cell maintenance by regulating proliferation, differentiation, and cell-fate decisions. Wnt signaling has also been implicated in a variety of cancers and other diseases. Loss of the Wnt pathway negative regulator adenomatous polyposis coli (APC) is the hallmark of human colorectal cancers (CRC). Recent advances in high-throughput sequencing further reveal many novel recurrent Wnt pathway mutations in addition to the well-characterized APC and β-catenin mutations in CRC. Despite attractive strategies to develop drugs for Wnt signaling, major hurdles in therapeutic intervention of the pathway persist. Here we discuss the Wnt-activating mechanisms in CRC and review the current advances and challenges in drug discovery.

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