Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

SUBMITTER: Wium M

PROVIDER: S-EPMC6210017 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

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

Wium Martha M Paccez Juliano D JD Zerbini Luiz F LF

Cells 20181012 10

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 re ...[more]

PMID: 30322068

Similar Datasets

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers.

Project description:Methotrexate, a structural analogue of folic acid, is one of the most effective and extensively used drugs for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. In this paper, we take an overview of the present state of knowledge with regards to complex mechanisms of methotrexate action and its applications as immunosuppressive drug or chemotherapeutic agent in oncological combination therapy. In addition, the issue of the potential benefits of methotrexate in the development of neurological disorders in Alzheimer's disease or myasthenia gravis will be discussed.

| S-EPMC7279024 | biostudies-literature

The Role of TAM Receptors in Bone.

Project description:The TAM (TYRO3, MERTK, and AXL) family of receptor tyrosine kinases are pleiotropic regulators of adult tissue homeostasis maintaining organ integrity and self-renewal. Disruption of their homeostatic balance fosters pathological conditions like autoinflammatory or degenerative diseases including rheumatoid arthritis, lupus erythematodes, or liver fibrosis. Moreover, TAM receptors exhibit prominent cell-transforming properties, promoting tumor progression, metastasis, and therapy resistance in various cancer entities. Emerging evidence shows that TAM receptors are involved in bone homeostasis by regulating osteoblastic bone formation and osteoclastic bone resorption. Therefore, TAM receptors emerge as new key players of the regulatory cytokine network of osteoblasts and osteoclasts and represent accessible targets for pharmacologic therapy for a broad set of different bone diseases, including primary and metastatic bone tumors, rheumatoid arthritis, or osteoporosis.

| S-EPMC10779100 | biostudies-literature

Hallmarks of pancreatic cancer: spotlight on TAM receptors.

Project description:Pancreatic ductal adenocarcinoma (PDAC) represents the most prevalent type of pancreatic cancer and ranks among the most aggressive tumours, with a 5-year survival rate of less than 11%. Projections indicate that by 2030, it will become the second leading cause of cancer-related deaths. PDAC presents distinctive hallmarks contributing to its dismal prognosis: (i) late diagnosis, (ii) heterogenous and complex mutational landscape, (iii) high metastatic potential, (iv) dense fibrotic stroma, (v) immunosuppressive microenvironment, and (vi) high resistance to therapy. Mounting evidence has shown a role for TAM (Tyro3, AXL, MerTK) family of tyrosine kinase receptors in PDAC initiation and progression. This review aims to describe the impact of TAM receptors on the defining hallmarks of PDAC and discuss potential future directions using these proteins as novel biomarkers for early diagnosis and targets for precision therapy in PDAC, an urgent unmet clinical need.

| S-EPMC11367522 | biostudies-literature

TAM receptors and their ligand-mediated activation: Role in atherosclerosis.

Project description:TAM family tyrosine kinase receptors including Tyro3, Axl, and MerTK are the key efferocytosis receptors presenting on antigen-presenting cell that mediate the clearance of apoptotic cells. They are thought to regulate inflammatory diseases by modulating inflammatory response and efferocytosis. Recent studies have revealed novel roles of TAM receptors in the biosynthesis of specialized pro-resolving mediators (SPMs) and inflammation resolution. In this chapter, we discuss the central roles of TAM signaling in atherosclerosis focusing on their regulation in efferocytosis and inflammation resolution and highlight the unique therapeutic potential of SPMs in blocking the progression of atherosclerosis.

| S-EPMC7971185 | biostudies-literature

Understanding the Multifaceted Role of Neutrophils in Cancer and Autoimmune Diseases.

Project description:Neutrophils are one of the first immune cell types that are recruited to injury and infection site. As a vital component of the immune system, neutrophils are heterogeneous immune cells known to have phagocytic property and function in inflammation. Recent studies revealed that neutrophils play dual roles in tumor initiation, development, and progression. The multifunctional roles of neutrophils in diseases are mainly due to their production of different effector molecules under different conditions. N1 and N2 neutrophils or high density neutrophils (HDNs) and low density neutrophils (LDNs) have been used to distinguish neutrophils subpopulations with pro- vs. anti-tumor activity, respectively. Indeed, N1 and N2 neutrophils also represent immunostimulating and immunosuppressive subsets, respectively, in cancer. The emerging studies support their multifaceted roles in autoimmune diseases. Although such subsets are rarely identified in autoimmune diseases, some unique subsets of neutrophils, including low density granulocytes (LDGs) and CD177+ neutrophils, have been reported. Given the heterogeneity and functional plasticity of neutrophils, it is necessary to understand the phenotypical and functional features of neutrophils in disease status. In this article, we review the multifaceted activates of neutrophils in cancer and autoimmune diseases, which may support new classification of neutrophils to help understand their important functions in immune homeostasis and pathologies.

| S-EPMC6237929 | biostudies-other

Immunobiology of the TAM receptors.

Project description:Recent studies have revealed that the TAM receptor protein tyrosine kinases--TYRO3, AXL and MER--have pivotal roles in innate immunity. They inhibit inflammation in dendritic cells and macrophages, promote the phagocytosis of apoptotic cells and membranous organelles, and stimulate the maturation of natural killer cells. Each of these phenomena may depend on a cooperative interaction between TAM receptor and cytokine receptor signalling systems. Although its importance was previously unrecognized, TAM signalling promises to have an increasingly prominent role in studies of innate immune regulation.

| S-EPMC2856445 | biostudies-literature

TAM receptors Tyro3 and Mer as novel targets in colorectal cancer.

Project description:PurposeCRC remains the third most common cancer worldwide with a high 5-year mortality rate in advanced cases. Combined with chemotherapy, targeted therapy is an additional treatment option. However as CRC still escapes targeted therapy the vigorous search for new targets is warranted to increase patients´ overall survival.ResultsIn this study we describe a new role for Gas6/protein S-TAM receptor interaction in CRC. Gas6, expressed by tumor-infiltrating M2-like macrophages, enhances malignant properties of tumor cells including proliferation, invasion and colony formation. Upon chemotherapy macrophages increase Gas6 synthesis, which significantly attenuates the cytotoxic effect of 5-FU chemotherapy on tumor cells. The anti-coagulant protein S has similar effects as Gas6.In CRC patient samples Tyro3 was overexpressed within the tumor. In-vitro inhibition of Tyro3 and Mer reduces tumor cell proliferation and sensitizes tumor cells to chemotherapy. Moreover high expression of Tyro3 and Mer in tumor tissue significantly shortens CRC patients´ survival.Experimental designVarious in vitro models were used to investigate the role of Gas6 and its TAM receptors in human CRC cells, by stimulation (rhGas6) and knockdown (siRNA) of Axl, Tyro3 and Mer. In terms of a translational research, we additionally performed an expression analysis in human CRC tissue and analyzed the medical record of these patients.ConclusionsTyro3 and Mer represent novel therapeutic targets in CRC and warrant further preclinical and clinical investigation in the future.

| S-EPMC5302919 | biostudies-literature

Targeting the TAM Receptors in Leukemia.

Project description:Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma. TAM receptors contribute to leukemic phenotypes through activation of pro-survival signaling pathways and interplay with other oncogenic proteins such as FLT3, LYN, and FGFR3. The TAM receptors also contribute to resistance to both cytotoxic chemotherapeutics and targeted agents, making them attractive therapeutic targets. A number of translational strategies for TAM inhibition are in development, including small molecule inhibitors, ligand traps, and monoclonal antibodies. Emerging areas of research include modulation of TAM receptors to enhance anti-tumor immunity, potential roles for TYRO-3 in leukemogenesis, and the function of the bone marrow microenvironment in mediating resistance to TAM inhibition.

| S-EPMC5126761 | biostudies-literature

Two-Front War on Cancer-Targeting TAM Receptors in Solid Tumour Therapy.

Project description:Receptor tyrosine kinases (RTKs) are transmembrane receptors that bind growth factors and cytokines and contain a regulated kinase activity within their cytoplasmic domain. RTKs play an important role in signal transduction in both normal and malignant cells, and their encoding genes belong to the most frequently affected genes in cancer cells. The TAM family proteins (TYRO3, AXL, and MERTK) are involved in diverse biological processes: immune regulation, clearance of apoptotic cells, platelet aggregation, cell proliferation, survival, and migration. Recent studies show that TAMs share overlapping functions in tumorigenesis and suppression of antitumour immunity. MERTK and AXL operate in innate immune cells to suppress inflammatory responses and promote an immunosuppressive tumour microenvironment, while AXL expression correlates with epithelial-to-mesenchymal transition, metastasis, and motility in tumours. Therefore, TAM RTKs represent a dual target in cancer due to their intrinsic roles in tumour cell survival, migration, chemoresistance, and their immunosuppressive roles in the tumour microenvironment (TME). In this review, we discuss the potential of TAMs as emerging therapeutic targets in cancer treatment. We critically assess and compare current approaches to target TAM RTKs in solid tumours and the development of new inhibitors for both extra- and intracellular domains of TAM receptor kinases.

| S-EPMC9140196 | biostudies-literature

Dual-Directional Immunomodulatory Effects of Corbrin Capsule on Autoimmune Thyroid Diseases.

Project description:Purpose. To investigate the effects of Corbrin Capsule (CS-C-Q80), a drug derived from Cordyceps sinensis (Berk.) Sacc., on autoimmune thyroid diseases (AITD). Methods. 44 Patients with Graves's disease (GD) and 56 patients with Hashimoto's thyroiditis (HT) were randomly assigned to treatment group (GD-Tx and HT-Tx) or control group (GD-Ct and HT-Ct). The control groups were given methimazole or levothyroxine only while the treatment groups were given Corbrin Capsule (2.0 g tid) besides the same conventional prescriptions as control groups. Thyroid hormones, thyroid antibodies, and T lymphocyte subsets were quantified at baseline and 24 weeks posttreatment. Results. Significant drop of serum anti-TPO-Ab levels was observed in both GD-Tx and HT-Tx groups. Before treatment, GD patients had higher helper T cells compared to cytotoxic T cells, while HT patients suffered from a nearly inverted proportion of helper T/cytotoxic T cells. There was a significant drop of the helper T/cytotoxic T cells ratio in GD-Tx to the median of the normal ranges after Corbrin treatment for 24 weeks, while that in HT-Tx was elevated. Conclusion. Corbrin Capsule could restore the balance between helper T and cytotoxic T cells in both GD and HT patients with dual-directional immunomodulatory effects. And it could significantly reduce the autoantibody levels in both GD and HT.

| S-EPMC5045992 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data