scholarly journals The Dual Role of TAM Receptors in Autoimmune Diseases and Cancer: An Overview

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 166 ◽  
Author(s):  
Martha Wium ◽  
Juliano Paccez ◽  
Luiz Zerbini
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Tyrosine Kinases ◽  
Therapeutic Potential ◽  
Cellular Processes ◽  
Tam Receptors ◽  
Different Types ◽  
Extracellular Environment ◽  
Migration And Development

Receptor tyrosine kinases (RTKs) regulate cellular processes by converting signals from the extracellular environment to the cytoplasm and nucleus. Tyro3, Axl, and Mer (TAM) receptors form an RTK family that plays an intricate role in tissue maintenance, phagocytosis, and inflammation as well as cell proliferation, survival, migration, and development. Defects in TAM signaling are associated with numerous autoimmune diseases and different types of cancers. Here, we review the structure of TAM receptors, their ligands, and their biological functions. We discuss the role of TAM receptors and soluble circulating TAM receptors in the autoimmune diseases systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Lastly, we discuss the effect of TAM receptor deregulation in cancer and explore the therapeutic potential of TAM receptors in the treatment of diseases.

scholarly journals Extracellular Vesicles From SDHB Deficient hPheo1 Cells Activate STAT3 in Wild-Type Cells

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A68-A69
Author(s):  
Hans K Ghayee ◽  
Sujal Patel ◽  
Kubra M Tuna ◽  
Lauren Liu ◽  
Yiling Xu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Extracellular Vesicles ◽  
Tyrosine Kinases ◽  
Wild Type ◽  
Cellular Processes ◽  
Transmission Electron ◽  
Different Types ◽  
Inactivating Mutations ◽  
Human Wild Type

Abstract Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that originate from the adrenal medulla and extra-adrenal paraganglia, respectively. Inactivating mutations in succinate dehydrogenase (SDHx) genes leads to succinate accumulation, increased HIF1-α levels, and uncontrollable growth of PPGLs. We hypothesized that small extracellular vesicles (EVs) released from progenitor cells derived from pheochromocytoma (hPheo1) with a shRNA mediated knockdown of SDHB are enriched in succinate metabolites that play a key role in the activation of various tyrosine dependent signaling pathways that are involved in turmorigenesis and proliferation. We isolated EVs from the conditioned media of human wild-type hPheo1 cells and hPheo1 cells with shRNA SDHB knockdown. The EVs from three separate preparations of each group were characterized by nanoparticle tracking analysis, transmission electron microscopy, and Western blotting using antibodies against different types of EV and one non-EV marker. Our results show small EVs from the SDHB knockdown hPheo1 cells increased the activation of phosphotyrosine residues in wild-type cells compared to cells treated with control EVs from the same cell type. Additionally, our data show these EVs increase phospho-STAT3 compared to the control EVs (3843.10 +/- 1138.89 vs. 213.65+/- 40.75; p<0.05; n=3) in cultured wild-type hPheo1 cells. Protein tyrosine kinases (PTKs) control various cellular processes including growth, differentiation, and metabolism by activating various signaling pathways including STAT3. The significance of these findings is that in some cancers, elevated succinate from a SDHx mutation has been shown to activate STAT3 which may explain a possible pathway for tumorigenesis. Studies from other investigators have shown that STAT3 expression is elevated in malignant PPGL tissues. Through enriched EV analysis our findings have confirmed the role of STAT3 in SDHB deficient cells. Additional studies are needed to identify other metabolites that are enriched in EVs that regulate phosphorylation of tyrosine residues and STAT3 activation.

Dysregulation of HOX as a Potential Therapeutic Target in Breast Cancer

2020 ◽  
Vol 27 ◽  
Author(s):  
Ji-Yeon Lee ◽  
Myoung Hee Kim
Keyword(s):  
Breast Cancer ◽  
Hox Genes ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Genome Structure ◽  
Control Cell ◽  
Three Dimensional ◽  
Cellular Processes ◽  
Hox Protein

: HOX genes belong to the highly conserved homeobox superfamily, responsible for the regulation of various cellular processes that control cell homeostasis, from embryogenesis to carcinogenesis. The abnormal expression of HOX genes is observed in various cancers, including breast cancer; they act as oncogenes or as suppressors of cancer, according to context. In this review, we analyze HOX gene expression patterns in breast cancer and examine their relationship, based on the three-dimensional genome structure of the HOX locus. The presence of non-coding RNAs, embedded within the HOX cluster, and the role of these molecules in breast cancer have been reviewed. We further evaluate the characteristic activity of HOX protein in breast cancer and its therapeutic potential.

Classic and Novel Signaling Pathways Involved in Cancer: Targeting the NF-κB and Syk Signaling Pathways

2019 ◽  
Vol 14 (3) ◽  
pp. 219-225 ◽  
Author(s):  
Cong Tang ◽  
Guodong Zhu
Keyword(s):  
Cancer Therapy ◽  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Cell Receptor ◽  
Transmembrane Receptors ◽  
Biological Responses ◽  
Different Types

The nuclear factor kappa B (NF-κB) consists of a family of transcription factors involved in the regulation of a wide variety of biological responses. Growing evidence support that NF-κB plays a major role in oncogenesis as well as its well-known function in the regulation of immune responses and inflammation. Therefore, we made a review of the diverse molecular mechanisms by which the NF-κB pathway is constitutively activated in different types of human cancers and the potential role of various oncogenic genes regulated by this transcription factor in cancer development and progression. We also discussed various pharmacological approaches employed to target the deregulated NF-κB signaling pathway and their possible therapeutic potential in cancer therapy. Moreover, Syk (Spleen tyrosine kinase), non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immune-receptors like the B-cell receptor (BCR), which can also activate the inflammasome and NF-κB-mediated transcription of chemokines and cytokines in the presence of pathogens would be discussed as well. The highlight of this review article is to summarize the classic and novel signaling pathways involved in NF-κB and Syk signaling and then raise some possibilities for cancer therapy.

scholarly journals The Role of Non-Coding RNAs in the Regulation of the Proto-Oncogene MYC in Different Types of Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 921
Author(s):  
Ekaterina Mikhailovna Stasevich ◽  
Matvey Mikhailovich Murashko ◽  
Lyudmila Sergeevna Zinevich ◽  
Denis Eriksonovich Demin ◽  
Anton Markovich Schwartz
Keyword(s):  
Malignant Tumors ◽  
Current Data ◽  
Cellular Processes ◽  
Cell Divisions ◽  
Specific Tumor ◽  
Different Types ◽  
Myc Gene ◽  
Non Coding Rnas ◽  
Tumor Types

Alterations in the expression level of the MYC gene are often found in the cells of various malignant tumors. Overexpressed MYC has been shown to stimulate the main processes of oncogenesis: uncontrolled growth, unlimited cell divisions, avoidance of apoptosis and immune response, changes in cellular metabolism, genomic instability, metastasis, and angiogenesis. Thus, controlling the expression of MYC is considered as an approach for targeted cancer treatment. Since c-Myc is also a crucial regulator of many cellular processes in healthy cells, it is necessary to find ways for selective regulation of MYC expression in tumor cells. Many recent studies have demonstrated that non-coding RNAs play an important role in the regulation of the transcription and translation of this gene and some RNAs directly interact with the c-Myc protein, affecting its stability. In this review, we summarize current data on the regulation of MYC by various non-coding RNAs that can potentially be targeted in specific tumor types.

scholarly journals Stem Cell Therapy and Regenerative Medicine in Autoimmune Diseases

2021 ◽  
Author(s):  
Bhuvaneshwari Sampath ◽  
Priyadarshan Kathirvelu ◽  
Kavitha Sankaranarayanan
Keyword(s):  
Stem Cell ◽  
Immune System ◽  
Regenerative Medicine ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoimmune Condition ◽  
Recent Trends

The role of immune system in our body is to defense against the foreign bodies. However, if the immune system fails to recognize self and non-self-cells in our body leads to autoimmune diseases. Widespread autoimmune diseases are rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, and more yet to be added to the list. This chapter discusses about how stem cell-based therapies and advancement of regenerative medicine endow with novel treatment for autoimmune diseases. Furthermore, in detail, specific types of stem cells and their therapeutic approach for each autoimmune condition along with their efficiency to obtain desired results are discussed. Ultimately, this chapter describes the recent trends in treating autoimmune diseases effectively using advanced stem cell research.

scholarly journals The Protective Role of HLA-DRB113 in Autoimmune Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Andreia Bettencourt ◽  
Cláudia Carvalho ◽  
Bárbara Leal ◽  
Sandra Brás ◽  
Dina Lopes ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Genetic Background ◽  
Protective Role ◽  
Negative Association ◽  
Thymic Selection ◽  
Systemic Lupus ◽  
Clonal Deletion ◽  
Drb1 Locus

Autoimmune diseases (AIDs) are characterized by a multifactorial aetiology and a complex genetic background, with the MHC region playing a major role. We genotyped for HLA-DRB1 locus 1228 patients with AIDs-213 with Systemic Lupus Erythematosus (SLE), 166 with Psoriasis or Psoriatic Arthritis (Ps + PsA), 153 with Rheumatoid Arthritis (RA), 67 with Systemic Sclerosis (SSc), 536 with Multiple Sclerosis (MS), and 93 with Myasthenia Gravis (MG) and 282 unrelated controls. We confirmed previously established associations of HLA-DRB115 (OR = 2.17) and HLA-DRB103 (OR = 1.81) alleles with MS, HLA-DRB103 with SLE (OR = 2.49), HLA-DRB101 (OR = 1.79) and HLA-DRB104 (OR = 2.81) with RA, HLA-DRB107 with Ps + PsA (OR = 1.79), HLA-DRB101 (OR = 2.28) and HLA-DRB108 (OR = 3.01) with SSc, and HLA-DRB103 with MG (OR = 2.98). We further observed a consistent negative association of HLA-DRB113 allele with SLE, Ps + PsA, RA, and SSc (18.3%, 19.3%, 16.3%, and 11.9%, resp., versus 29.8% in controls). HLA-DRB113 frequency in the AIDs group was 20.0% (OR = 0.58). Although different alleles were associated with particular AIDs, the same allele, HLA-DRB113, was underrepresented in all of the six diseases analysed. This observation suggests that this allele may confer protection for AIDs, particularly for systemic and rheumatic disease. The protective effect of HLA-DRB113 could be explained by a more proficient antigen presentation by these molecules, favouring efficient clonal deletion during thymic selection.

scholarly journals Mending a broken heart: the role of mitophagy in cardioprotection

2015 ◽  
Vol 308 (3) ◽  
pp. H183-H192 ◽  
Author(s):  
Alexandra G. Moyzis ◽  
Junichi Sadoshima ◽  
Åsa B. Gustafsson
Keyword(s):  
Heart Failure ◽  
Therapeutic Potential ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Cellular Processes ◽  
Differentiated Cells ◽  
Calcium Storage ◽  
Response To Stress ◽  
Metabolite Synthesis ◽  
Energy Dependent

The heart is highly energy dependent with most of its energy provided by mitochondrial oxidative phosphorylation. Mitochondria also play a role in many other essential cellular processes including metabolite synthesis and calcium storage. Therefore, maintaining a functional population of mitochondria is critical for cardiac function. Efficient degradation and replacement of dysfunctional mitochondria ensures cell survival, particularly in terminally differentiated cells such as cardiac myocytes. Mitochondria are eliminated via mitochondrial autophagy or mitophagy. In the heart, mitophagy is an essential housekeeping process and required for cardiac homeostasis. Reduced autophagy and accumulation of impaired mitochondria have been linked to progression of heart failure and aging. In this review, we discuss the pathways that regulate mitophagy in cells and highlight the cardioprotective role of mitophagy in response to stress and aging. We also discuss the therapeutic potential of targeting mitophagy and directions for future investigation.

scholarly journals The Histone Modification Code in the Pathogenesis of Autoimmune Diseases

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yasuto Araki ◽  
Toshihide Mimura
Keyword(s):  
Autoimmune Diseases ◽  
Histone Modifications ◽  
Lupus Erythematosus ◽  
Cell Types ◽  
Biliary Cirrhosis ◽  
Loss Of Self ◽  
Self Tolerance ◽  
Different Cell Types

Autoimmune diseases are chronic inflammatory disorders caused by a loss of self-tolerance, which is characterized by the appearance of autoantibodies and/or autoreactive lymphocytes and the impaired suppressive function of regulatory T cells. The pathogenesis of autoimmune diseases is extremely complex and remains largely unknown. Recent advances indicate that environmental factors trigger autoimmune diseases in genetically predisposed individuals. In addition, accumulating results have indicated a potential role of epigenetic mechanisms, such as histone modifications, in the development of autoimmune diseases. Histone modifications regulate the chromatin states and gene transcription without any change in the DNA sequence, possibly resulting in phenotype alteration in several different cell types. In this paper, we discuss the significant roles of histone modifications involved in the pathogenesis of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary biliary cirrhosis, and type 1 diabetes.

scholarly journals A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Mie Oki ◽  
Norihiko Watanabe ◽  
Takayoshi Owada ◽  
Yoshihiro Oya ◽  
Kei Ikeda ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
T Lymphocyte ◽  
Lupus Erythematosus ◽  
Susceptibility Gene ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Immunological Homeostasis ◽  
Deficient Mice

Inhibitory coreceptors are thought to play important roles in maintaining immunological homeostasis, and a defect in the negative signals from inhibitory coreceptors may lead to the development of autoimmune diseases. We have recently identified B and T lymphocyte attenuator (BTLA), a new inhibitory coreceptor expressed on immune cells, and we suggest that BTLA may be involved in the development of autoimmune diseases using BTLA-deficient mice. However, the role of BTLA in the pathogenesis of autoimmune diseases in humans remains unknown. We, therefore, examined the possible association between BTLA and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) by conducting a case-control genetic association study. We found that 590C single-nucleotide polymorphism (SNP) of BTLA gene was significantly associated with susceptibility to RA, but not to SLE or SS. Furthermore, RA patients bearing this 590C SNP developed the disease significantly earlier than the patients without this allele. We also found that BTLA with 590C allele lacked the inhibitory activity on concanavalin A- and anti-CD3 Ab-induced IL-2 production in Jurkat T cells. These results suggest that BTLA is an RA-susceptibility gene and is involved in the protection from autoimmunity in humans.

scholarly journals Therapeutic Potential of IL-9 in Allergic and Autoimmune Diseases

2021 ◽  
Author(s):  
Ahmed Ummey Khalecha Bintha ◽  
Amani Souwelimatou Amadou ◽  
Mursalin Md Huzzatul ◽  
Muhammad Fauziyya
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Autoimmune Diseases ◽  
Therapeutic Potential ◽  
Cell Subset ◽  
Allergic Diseases ◽  
Helper T Cell ◽  
T Cell Subset ◽  
Interleukin 9

Interleukin-9 (IL-9) is a pleiotropic cytokine produced by several immune and epithelial cells. Recently, many studies have eluded the physiological and pathological roles of IL-9 and its lineage-specific helper T cell subset (Th9). In this chapter, we will focus on the immunological role of Interleukin 9 (IL-9) in allergy and autoimmunity. We will introduce the basics of IL-9 and describe the cells involved in the secretion, signaling, and regulation of IL-9. After establishing the background, we will discuss the pathogenesis and regulation of IL-9 in allergic and autoimmune diseases. We will conclude the chapter by providing an updated therapeutics that target IL-9 and their potential uses in autoimmune and allergic diseases.

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