scholarly journals The Emerging Role of TYRO3 as a Therapeutic Target in Cancer

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 474 ◽  
Author(s):  
Sherri Smart ◽  
Eleana Vasileiadi ◽  
Xiaodong Wang ◽  
Deborah DeRyckere ◽  
Douglas Graham
Keyword(s):  
Immune Regulation ◽  
Therapeutic Target ◽  
Tyrosine Kinases ◽  
Biological Processes ◽  
Breast Cancers ◽  
Tumor Cell Survival ◽  
Promote Tumor Cell ◽  
And Migration ◽  
Resistance To Chemotherapy

The TAM family (TYRO3, AXL, MERTK) tyrosine kinases play roles in diverse biological processes including immune regulation, clearance of apoptotic cells, platelet aggregation, and cell proliferation, survival, and migration. While AXL and MERTK have been extensively studied, less is known about TYRO3. Recent studies revealed roles for TYRO3 in cancer and suggest TYRO3 as a therapeutic target in this context. TYRO3 is overexpressed in many types of cancer and functions to promote tumor cell survival and/or proliferation, metastasis, and resistance to chemotherapy. In addition, higher levels of TYRO3 expression have been associated with decreased overall survival in patients with colorectal, hepatocellular, and breast cancers. Here we review the physiological roles for TYRO3 and its expression and functions in cancer cells and the tumor microenvironment, with emphasis on the signaling pathways that are regulated downstream of TYRO3 and emerging roles for TYRO3 in the immune system. Translational agents that target TYRO3 are also described.

scholarly journals SUN-734 The Role of Chromatin-Associated LncRNA161 in Estrogen-Dependent Transcription

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ilene Le ◽  
Ramesh Choudhari ◽  
Barbara Yang ◽  
Enrique I Ramos ◽  
Melina Sedano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Transcriptional Activation ◽  
Therapeutic Target ◽  
Estrogen Signaling ◽  
Tumor Proliferation ◽  
Biological Processes ◽  
Breast Cancers ◽  
Potential Therapeutic Target

Abstract Long noncoding RNAs (lncRNAs) have been identified to play a role in the progression of many different types of cancer. Some biological processes that are involved with lncRNA include but are not limited to chromatin organization, transcriptional and post-transcriptional gene expression, and protein and transcript trafficking. When lncRNAs are aberrantly expressed, disruption in the biological processes can cause tumor proliferation and progression leading to cancers. Studies have shown the role of lncRNAs in association with breast cancers. While estrogen receptor alpha positive (ERα+) breast cancer responds well to anti-estrogen treatment, the cancer can become refractory. With breast cancer as one of the leading causes of mortality in women, deeper understanding of lncRNAs can establish it as a potential therapeutic target. It will be determined the functional mechanisms by which lncRNAs, specifically lncRNA161, drives hormone-resistance in breast cancer. LncRNA161 was selected from a comprehensive list of lncRNAs due to it being expressed in reproductive tissue, being tamoxifen resistant, being robustly regulated by estrogen, and its association with the chromatin. It was determined that lncRNA161 was upregulated in breast cancers. When lncRNA161 was treated with estrogen, there was transcriptional activation and localization to the chromatin. Subsequent knockdown of lncRNA161 affected other genes in the estrogen signaling pathway. Overexpression of lncRNA161 demonstrated increased proliferation, and knockdown showed decreased proliferation indicating a role of lncRNA161 in tumor proliferation and progression in breast cancer. Altogether, the results suggest lncRNA161’s involvement in the estrogen signaling pathway and establish it as a potential therapeutic target in hormone-refractory breast cancer. Supported by grant from the Cancer Prevention and Research Institute of Texas to S.S.G.

scholarly journals The Role of Phosphotyrosine Signaling Pathway in Parotid Gland Proliferation and Function

1995 ◽  
Vol 6 (2) ◽  
pp. 119-131 ◽  
Author(s):  
K.R. Purushotham ◽  
M.G. Humphreys-Beher
Keyword(s):  
Salivary Glands ◽  
Tyrosine Kinases ◽  
Intracellular Signaling ◽  
Potential Role ◽  
Biological Processes ◽  
Secretory Function ◽  
Phosphotyrosine Signaling ◽  
And Function ◽  
Active Proliferation

Tyrosine phosphorylation and the intracellular signaling processes associated with it have been the focus of intense study due to its importance in the regulation of biological processes as diverse as cell proliferation and cell differentiation. While much of what we now understand has been derived from the study of cell lines and tumor cells, the salivary glands provide a model to examine the effects of tyrosine kinases and tyrosine phosphatases in a normal differentiated tissue. This review will focus, therefore, on the role tyrosine kinases and phosphatases play in inducing the transition from stasis to active proliferation and their potential role in mediating secretory function of the salivary glands.

Role of CD73 in Disease: Promising Prognostic Indicator and Therapeutic Target

2018 ◽  
Vol 25 (19) ◽  
pp. 2260-2271 ◽  
Author(s):  
Jiayin Yang ◽  
Xiaohong Liao ◽  
Jerry Yu ◽  
Ping Zhou
Keyword(s):  
Therapeutic Target ◽  
Ischemia Reperfusion ◽  
Prognostic Indicator ◽  
Treg Cells ◽  
Inflammatory Factors ◽  
Endothelial Barrier Function ◽  
Inflammatory Phenotype ◽  
Multiple Cells ◽  
Resistance To Chemotherapy

CD73, also known as ecto-5’-nucleotidase (eN, NT5E, EC3.13.5), is the ratelimiting enzyme for adenosine generation and is expressed on multiple cells. Its expression is significantly influenced by hypoxia and inflammatory factors. During inflammation, CD73 protects endothelial barrier function and inhibits leukocyte trafficking. CD73 also promotes M2 macrophages (anti-inflammatory phenotype). In addition, CD73 is expressed on Treg cells and mediates immune suppression through adenosine. CD73 serves as an essential regulator for the immunity and inflammation. Its expression is related to many diseases, such as autoimmune diseases, ischemia-reperfusion injuries, arterial calcifications, and atherosclerosis. CD73 is overexpressed in many cancers. Its expression is positively associated with tumor growth, metastasis, angiogenesis, poor prognosis and resistance to chemotherapy. Thus, CD73 may be used for prognostic indicator and therapeutic target in diseases such as cancers.

scholarly journals Involvement of HMGB1 in Resistance to Tumor Vessel-Targeted, Monoclonal Antibody-Based Immunotherapy

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Vito Pistoia ◽  
Annalisa Pezzolo
Keyword(s):  
Monoclonal Antibody ◽  
Immune Regulation ◽  
High Mobility ◽  
Genomic Stability ◽  
Tumor Resistance ◽  
Tumor Vessel ◽  
Human Neuroblastoma ◽  
Molecular Patterns ◽  
Resistance To Chemotherapy

High mobility group box 1 (HMGB1) is a member of the “danger associated molecular patterns” (DAMPs) than can localize in various compartments of the cell (from the nucleus to the cell surface) and subserve different functions accordingly. HMGB1 is implicated in maintenance of genomic stability, autophagy, immune regulation, and tumor growth. HMGB1-induced autophagy promotes tumor resistance to chemotherapy, as shown in different models of malignancy, for example, osteosarcoma, leukemia, and gastric cancer. To the best of our knowledge, there is virtually no information on the relationships between HMGB1 and resistance to immunotherapy. A recent study from our group has shed new light on this latter issue. We have demonstrated that targeting of tumor-derived endothelial cells with an anti-human CD31 monoclonal antibody in a human neuroblastoma model was unsuccessful due to a complex chain of events involving the participation of HMGB1. These results are discussed in detail since they provide the first evidence for a role of HMGB1 in resistance of tumor cells to monoclonal antibody-based immunotherapy.

scholarly journals Sirt3 Exerts Its Tumor-Suppressive Role by Increasing p53 and Attenuating Response to Estrogen in MCF-7 Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 294 ◽  
Author(s):  
Marija Pinterić ◽  
Iva I. Podgorski ◽  
Marijana Popović Hadžija ◽  
Vedrana Filić ◽  
Mladen Paradžik ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Inhibitory Effect ◽  
Breast Cancers ◽  
Proliferative Effect ◽  
Er Positive ◽  
And Migration ◽  
Tumor Suppressive Function ◽  
Mcf 7

Estrogen (E2) is a major risk factor for the initiation and progression of malignancy in estrogen receptor (ER) positive breast cancers, whereas sirtuin 3 (Sirt3), a major mitochondrial NAD+-dependent deacetylase, has the inhibitory effect on the tumorigenic properties of ER positive MCF-7 breast cancer cells. Since it is unclear if this effect is mediated through the estrogen receptor alpha (ERα) signaling pathway, in this study, we aimed to determine if the tumor-suppressive function of Sirt3 in MCF-7 cells interferes with their response to E2. Although we found that Sirt3 improves the antioxidative response and mitochondrial fitness of the MCF-7 cells, it also increases DNA damage along with p53, AIF, and ERα expression. Moreover, Sirt3 desensitizes cells to the proliferative effect of E2, affects p53 by disruption of the ERα–p53 interaction, and decreases proliferation, colony formation, and migration of the cells. Our observations indicate that these tumor-suppressive effects of Sirt3 could be reversed by E2 treatment only to a limited extent which is not sufficient to recover the tumorigenic properties of the MCF-7 cells. This study provides new and interesting insights with respect to the functional role of Sirt3 in the E2-dependent breast cancers.

scholarly journals STAT3, the Challenge for Chemotherapeutic and Radiotherapeutic Efficacy

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2459
Author(s):  
Ping-Lian Yang ◽  
Lu-Xin Liu ◽  
En-Min Li ◽  
Li-Yan Xu
Keyword(s):  
Receptor Tyrosine Kinase ◽  
Feedback Loop ◽  
Target Genes ◽  
Dominant Negative ◽  
Negative Regulator ◽  
Biological Processes ◽  
Signal Transducer ◽  
Transcription 3 ◽  
Resistance To Chemotherapy

Chemoradiotherapy is one of the most effective and extensively used strategies for cancer treatment. Signal transducer and activator of transcription 3 (STAT3) regulates vital biological processes, such as cell proliferation and cell growth. It is constitutively activated in various cancers and limits the application of chemoradiotherapy. Accumulating evidence suggests that STAT3 regulates resistance to chemotherapy and radiotherapy and thereby impairs therapeutic efficacy by mediating its feedback loop and several target genes. The alternative splicing product STAT3β is often identified as a dominant-negative regulator, but it enhances sensitivity to chemotherapy and offers a new and challenging approach to reverse therapeutic resistance. We focus here on exploring the role of STAT3 in resistance to receptor tyrosine kinase (RTK) inhibitors and radiotherapy, outlining the potential of targeting STAT3 to overcome chemo(radio)resistance for improving clinical outcomes, and evaluating the importance of STAT3β as a potential therapeutic approach to overcomes chemo(radio)resistance. In this review, we discuss some new insights into the effect of STAT3 and its subtype STAT3β on chemoradiotherapy sensitivity, and we explore how these insights influence clinical treatment and drug development for cancer.

scholarly journals Role of Aquaporins in the Physiological Functions of Mesenchymal Stem Cells

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2678
Author(s):  
Antonella Zannetti ◽  
Gheorghe Benga ◽  
Arturo Brunetti ◽  
Francesco Napolitano ◽  
Luigi Avallone ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Mesenchymal Stem Cells ◽  
Water Channel ◽  
Biological Processes ◽  
Fluid Flux ◽  
Physiological Functions ◽  
Channel Proteins ◽  
And Migration

Aquaporins (AQPs) are a family of membrane water channel proteins that control osmotically-driven water transport across cell membranes. Recent studies have focused on the assessment of fluid flux regulation in relation to the biological processes that maintain mesenchymal stem cell (MSC) physiology. In particular, AQPs seem to regulate MSC proliferation through rapid regulation of the cell volume. Furthermore, several reports have shown that AQPs play a crucial role in modulating MSC attachment to the extracellular matrix, their spread, and migration. Shedding light on how AQPs are able to regulate MSC physiological functions can increase our knowledge of their biological behaviours and improve their application in regenerative and reparative medicine.

scholarly journals lncRNA HOXA11-AS Promotes Proliferation and Migration via Sponging miR-155 in Hypopharyngeal Squamous Cell Carcinoma

2020 ◽  
Vol 28 (3) ◽  
pp. 311-319
Author(s):  
Jianing Xu ◽  
Qiyu Bo ◽  
Xiang Zhang ◽  
Dapeng Lei ◽  
Jue Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Target ◽  
Luciferase Reporter ◽  
Hypopharyngeal Squamous Cell Carcinoma ◽  
Gene Assay ◽  
And Migration ◽  
Proliferation And Migration

Hypopharyngeal squamous cell carcinoma (HSCC) remains one of the most lethal malignancies in the head and neck. Long noncoding RNA (lncRNA) HOXA11-AS is proven to function as an oncogene and a therapeutic target in various tumors. Our previous study and others have demonstrated that HOXA11-AS is one of the most upregulated lncRNAs in HSCC. However, the role of HOXA11-AS in HSCC has not yet been identified. The current study demonstrated that the expression of HOXA11-AS was significantly upregulated in HSCC tumors and was positively associated with lymph node metastasis. Moreover, functional experiments revealed that HOXA11-AS knockdown suppressed the proliferation and migration potential in FaDu cells. Furthermore, luciferase reporter gene assay combined with cellular functional experiments demonstrated that HOXA11-AS functioned as a molecular sponge for miR-155, and inhibition of miR-155 attenuated the suppressive effect of HOXA11-AS knockdown on the aggressive phenotype in HSCC. This study identifies a tumor-promoting role of HOXA11-AS in HSCC and suggests HOXA11-AS might be a potential diagnostic and therapeutic target for HSCC.

scholarly journals Promising therapeutic role of miR-27b in tumor

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769165 ◽  
Author(s):  
Li Ding ◽  
Jie Ni ◽  
Fan Yang ◽  
Lingli Huang ◽  
Heng Deng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Therapeutic Target ◽  
Biological Pathways ◽  
Molecular Targeting ◽  
Gene Clustering ◽  
Biological Processes ◽  
Targeting Therapy ◽  
Human Cancers ◽  
Promising Therapeutic Target

MicroRNAs are small nonprotein-encoding RNAs ranging from 18 to 25 nucleotides in size and regulate multiple biological pathways via directly targeting a variety of associated genes in cancers. MicroRNA-27b is a highly conserved MicroRNA throughout vertebrates and there are two homologs (hsa-miR-27a and hsa-miR-27b) in humans. MicroRNA-27b is an intragenic microRNA located on chromosome 9q22.1 within the C9orf3 gene, clustering with miR-23b and miR-24-1 in human. As a frequently dysregulated microRNA in human cancers, microRNA-27b could function as a tumor suppressor or an oncogenic microRNA. More and more studies indicate that microRNA-27b is involved in affecting various biological processes, such as angiogenesis, proliferation, metastasis, and drug resistance, and thus may act as a promising therapeutic target in human cancers. In this review, we discuss the role of microRNA-27b in detail and offer novel insights into molecular targeting therapy for cancers.

Credit constraints and Rural Migration: Evidence from Six Villages in Uttar Pradesh

2018 ◽  
Vol 15 (3) ◽  
pp. 389-398
Author(s):  
Ruchi Singh
Keyword(s):  
Credit Constraints ◽  
Uttar Pradesh ◽  
Binary Logistic Regression ◽  
Binary Logistic Regression Model ◽  
Male Migration ◽  
Rural Economies ◽  
And Migration ◽  
The Relationship ◽  
The Empirical Analysis

Rural economies in developing countries are often characterized by credit constraints. Although few attempts have been made to understand the trends and patterns of male out-migration from Uttar Pradesh (UP), there is dearth of literature on the linkage between credit accessibility and male migration in rural Uttar Pradesh. The present study tries to fill this gap. The objective of this study is to assess the role of credit accessibility in determining rural male migration. A primary survey of 370 households was conducted in six villages of Jaunpur district in Uttar Pradesh. Simple statistical tools and a binary logistic regression model were used for analyzing the data. The result of the empirical analysis shows that various sources of credit and accessibility to them play a very important role in male migration in rural Uttar Pradesh. The study also found that the relationship between credit constraints and migration varies across various social groups in UP.

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