scholarly journals EGF-Activated Grb7 Confers to STAT3-Mediated EPHA4 Gene Expression in Regulating Lung Cancer Progression

2020 ◽  
Author(s):  
Pei-Yu Chu ◽  
Yu-Ling Tai ◽  
Ming-Yang Wang ◽  
Hsinyu Lee ◽  
Wen Hung Kuo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Cancer Progression ◽  
Growth Factor Receptor ◽  
Adaptor Protein ◽  
Nuclear Accumulation ◽  
Dependent Manner ◽  
Cellular Functions ◽  
Cancer Migration ◽  
Growth Factor Receptor Bound

AbstractGrowth factor receptor bound protein-7 (Grb7) is a multi-domain signaling adaptor protein that regulates various cellular functions acting as an adaptor protein in relaying signal transduction. Although several studies indicated that Grb7 amplifies EGFR-mediated signaling in cancers, the detailed regulatory mechanism of whether and how Grb7 is involved in EGFR-mediated lung cancer progression remains unclear. Here, we demonstrate that EGF-regulated Grb7 phosphorylation promotes lung cancer progression through phosphorylation of STAT3. Intrinsically, EGF/EGFR signal is required for the formation of Grb7/STAT3 complex as well as its nuclear accumulation. Once in the nucleus, STAT3 interacts with EPHA4 promoter, which in turn affects the gene expression level of EPHA4 through transcriptional regulation. Functionally, EphA4 together with EGFR promotes cancer migration, proliferation, and anchorage-independent growth. Our study reveals a novel mechanism in which Grb7 contribute to lung cancer malignancies through its interaction with STAT3 that leads to sequential regulation of EPHA4 gene expression in an EGF/EGFR signal-dependent manner.

scholarly journals Gene Expression and Transcriptome Profiling of Changes in a Cancer Cell Line Post-Exposure to Cadmium Telluride Quantum Dots: Possible Implications in Oncogenesis

Dose-Response ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 155932582110198
Author(s):  
Mohammed S. Aldughaim ◽  
Mashael R. Al-Anazi ◽  
Marie Fe F. Bohol ◽  
Dilek Colak ◽  
Hani Alothaid ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantum Dots ◽  
Cancer Cells ◽  
Cadmium Telluride ◽  
Cancer Progression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Dependent Manner ◽  
Cdte Qds ◽  
Cadmium Telluride Quantum Dots

Cadmium telluride quantum dots (CdTe-QDs) are acquiring great interest in terms of their applications in biomedical sciences. Despite earlier sporadic studies on possible oncogenic roles and anticancer properties of CdTe-QDs, there is limited information regarding the oncogenic potential of CdTe-QDs in cancer progression. Here, we investigated the oncogenic effects of CdTe-QDs on the gene expression profiles of Chang cancer cells. Chang cancer cells were treated with 2 different doses of CdTe-QDs (10 and 25 μg/ml) at different time intervals (6, 12, and 24 h). Functional annotations helped identify the gene expression profile in terms of its biological process, canonical pathways, and gene interaction networks activated. It was found that the gene expression profiles varied in a time and dose-dependent manner. Validation of transcriptional changes of several genes through quantitative PCR showed that several genes upregulated by CdTe-QD exposure were somewhat linked with oncogenesis. CdTe-QD-triggered functional pathways that appear to associate with gene expression, cell proliferation, migration, adhesion, cell-cycle progression, signal transduction, and metabolism. Overall, CdTe-QD exposure led to changes in the gene expression profiles of the Chang cancer cells, highlighting that this nanoparticle can further drive oncogenesis and cancer progression, a finding that indicates the merit of immediate in vivo investigation.

scholarly journals Bivalent Genes Targeting of Glioma Heterogeneity and Plasticity

2021 ◽  
Vol 22 (2) ◽  
pp. 540
Author(s):  
Mariam Markouli ◽  
Dimitrios Strepkos ◽  
Kostas A. Papavassiliou ◽  
Athanasios G. Papavassiliou ◽  
Christina Piperi
Keyword(s):  
Gene Expression ◽  
Cancer Progression ◽  
Integration Site ◽  
Survival Rates ◽  
Family Members ◽  
Therapy Resistance ◽  
Cellular Functions ◽  
Cns Neoplasms ◽  
Development Regulation

Gliomas account for most primary Central Nervous System (CNS) neoplasms, characterized by high aggressiveness and low survival rates. Despite the immense research efforts, there is a small improvement in glioma survival rates, mostly attributed to their heterogeneity and complex pathophysiology. Recent data indicate the delicate interplay of genetic and epigenetic mechanisms in regulating gene expression and cell differentiation, pointing towards the pivotal role of bivalent genes. Bivalency refers to a property of chromatin to acquire more than one histone marks during the cell cycle and rapidly transition gene expression from an active to a suppressed transcriptional state. Although first identified in embryonal stem cells, bivalent genes have now been associated with tumorigenesis and cancer progression. Emerging evidence indicates the implication of bivalent gene regulation in glioma heterogeneity and plasticity, mainly involving Homeobox genes, Wingless-Type MMTV Integration Site Family Members, Hedgehog protein, and Solute Carrier Family members. These genes control a wide variety of cellular functions, including cellular differentiation during early organism development, regulation of cell growth, invasion, migration, angiogenesis, therapy resistance, and apoptosis. In this review, we discuss the implication of bivalent genes in glioma pathogenesis and their potential therapeutic targeting options.

scholarly journals Systemic Platelet-activating Factor Receptor Activation Augments Experimental Lung Tumor Growth and Metastasis

2014 ◽  
Vol 7 ◽  
pp. CGM.S14501 ◽  
Author(s):  
Patrick C. Hackler ◽  
Sarah Reuss ◽  
Raymond L. Konger ◽  
Jeffrey B. Travers ◽  
Ravi P. Sahu
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Lung Tumor ◽  
Platelet Activating Factor ◽  
Receptor Activation ◽  
Dependent Manner ◽  
Melanoma Tumor ◽  
Tumor Growth And Metastasis ◽  
The Impact

Pro-oxidative stressors including cigarette smoke (CS) generate novel lipids with platelet-activated factor-receptor (PAF-R) agonistic activity mediate systemic immunosuppression, one of the most recognized events in promoting carcinogenesis. Our previous studies have established that these oxidized-PAF-R-agonists augment murine B16F10 melanoma tumor growth in a PAF-R-dependent manner because of its effects on host immunity. As CS generates PAF-R agonists, the current studies sought to determine the impact of PAF-R agonists on lung cancer growth and metastasis. Using the murine Lewis Lung Carcinoma (LLC1) model, we demonstrate that treatment of C57BL/6 mice with a PAF-R agonist augments tumor growth and lung metastasis in a PAF-R-dependent manner as these findings were not seen in PAF-R-deficient mice. Importantly, this effect was because of host rather than tumor cells PAF-R dependent as LLC1 cells do not express functional PAF-R. These findings indicate that experimental lung cancer progression can be modulated by the PAF system.

Signal Transducer and Activator of Transcription6 Signaling Pathway in Tumor-Associated Macrophage Aggravates Lung Cancer Progression

2021 ◽  
Vol 11 (9) ◽  
pp. 1707-1713
Author(s):  
Jun Wan ◽  
Jian Wang ◽  
Qiurong Huang ◽  
Guanggui Ding ◽  
Xiean Ling
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
T Cell ◽  
Cancer Progression ◽  
Cancer Tissue ◽  
M2 Macrophage ◽  
Normal Tissues ◽  
Tumor Associated Macrophage ◽  
M1 Macrophage ◽  
And Migration

Lung cancer is a most common cancer worldwide. Tumor-associated macrophage (TAM) is known a key effector cell in tumor microenvironment. Meanwhile, STAT6 is crucial to cancer development. We aimed to determine the interaction between STAT6 and TAMs in lung cancer. In this work, firstly, we established mouse model of lung cancer. Then, immunofluorescence was performed to determine STAT6 and CD206 level in lung cancer tissue and adjacent normal tissues as well as model mice. RT-qPCR was applied to detect differentiation of macrophage and determine related gene expression. After treatment of siRNA of STAT6 or STAT6 inhibitor (AS1517499), Transwell assay and MTT were used to determine cell proliferation and migration. STAT6 was upregulated in lung cancer tissues while arginase was more active in M2 macrophage rather than M1 macrophage. Transfection of si-STAT6 not only decreased differentiation in M2 macrophage but also inhibited proliferative, migratory and invasive ability of cancer cells while AS1517499 led to reduced tumor growth. STAT6 inhibition caused decreased expression of M2 macrophages. Similarly, intratumoral T cell markers showed that CD8+T cell gene expression and CD4-mediated T cell marker FoxP3 was increased slightly. Taken altogether, macrophage-STAT6 promotes cell migration and proliferation in lung cancer.

scholarly journals Dysfunction of GRAP, encoding the GRB2-related adaptor protein, is linked to sensorineural hearing loss

2019 ◽  
Vol 116 (4) ◽  
pp. 1347-1352 ◽  
Author(s):  
Chong Li ◽  
Guney Bademci ◽  
Asli Subasioglu ◽  
Oscar Diaz-Horta ◽  
Yi Zhu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Factor Receptor ◽  
Adaptor Protein ◽  
Adaptor Proteins ◽  
Ras Signaling ◽  
Nonsyndromic Deafness ◽  
Auditory Hair Cells ◽  
Cytoskeleton Dynamics ◽  
Growth Factor Receptor Bound

We have identified a GRAP variant (c.311A>T; p.Gln104Leu) cosegregating with autosomal recessive nonsyndromic deafness in two unrelated families. GRAP encodes a member of the highly conserved growth factor receptor-bound protein 2 (GRB2)/Sem-5/drk family of proteins, which are involved in Ras signaling; however, the function of the growth factor receptor-bound protein 2 (GRB2)-related adaptor protein (GRAP) in the auditory system is not known. Here, we show that, in mouse, Grap is expressed in the inner ear and the protein localizes to the neuronal fibers innervating cochlear and utricular auditory hair cells. Downstream of receptor kinase (drk), the Drosophila homolog of human GRAP, is expressed in Johnston’s organ (JO), the fly hearing organ, and the loss of drk in JO causes scolopidium abnormalities. drk mutant flies present deficits in negative geotaxis behavior, which can be suppressed by human wild-type but not mutant GRAP. Furthermore, drk specifically colocalizes with synapsin at synapses, suggesting a potential role of such adaptor proteins in regulating actin cytoskeleton dynamics in the nervous system. Our findings establish a causative link between GRAP mutation and nonsyndromic deafness and suggest a function of GRAP/drk in hearing.

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