Abstract Background Cysteine-containing leukotrienes (cysteinyl-LTs) are pivotal inflammatory mediators that play important roles in the pathophysiology of asthma, allergic rhinitis, and other conditions. In particular, cysteinyl-LTs exert a variety effects with relevance to aetiology asthma such as smooth muscle contraction, eosinophil recruitment, increased microvascular permeability, enhanced mucus secretion decreased transport and, finally, airway cells (ASMC) proliferation. We used...

Phospholipase Cepsilon (PLCepsilon) has been suggested to transduce signals from small GTPases, but its biological function not yet clarified. Using astrocytes PLCepsilon-deficient mice, we demonstrate that endogenous G protein-coupled receptors (GPCRs) for lysophosphatidic acid, sphingosine 1-phosphate, and thrombin regulate phosphoinositide hydrolysis primarily through PLCepsilon. Stimulation by lysophospholipids occurs G(i), whereas activates PLC Rho. Further studies reveal PLCepsilon is...

Histone deacetylase 1 (HDAC1) is an important epigenetic controller involved in transcriptional regulation through modification of chromatin structure. Genetic and changes deregulation signal transduction pathways have been implicated the development breast cancer. Downregulation estrogen receptor α (ERα) expression one mechanisms behind acquisition endocrine resistance. Sustained increased hormone growth factor signaling cancer cells contribute to resistance therapy. Both HDACs PI3K/mTOR...

Both cysteinyl-leukotrienes and extracellular nucleotides mediate inflammatory responses via specific G-protein-coupled receptors, the CysLT P2Y respectively. Since these mediators accumulate at sites of inflammation, cells express both classes their are likely to be crossregulated. We investigated molecular basis desensitization trafficking CysLT1 receptor constitutively transiently expressed in human monocyte/macrophage-like U937 or COS-7 response LTD4 nucleotides. Exposure agonist induced...

Histone deacetylase 1 (HDAC1) is an essential epigenetic regulator belonging to a highly conserved family of deacetylases. Increased HDAC1 activity and expression often correlates with neoplastic transformation. Here we show how specific modification by SUMO1, but not SUMO2, facilitates degradation. Our findings reveal that conjugation promotes ubiquitination This suggested the observation in non-tumorigenic mammary epithelial cells preferentially conjugated SUMO1 leading proteolysis,...

Epidermal growth factor receptor (EGFR) overexpression is associated with the development of head and neck cancer (HNC) represents one main therapeutic targets for this disease. The use EGFR inhibitors has limited efficacy due to their primary acquired resistance, partially because increased epithelial mesenchymal transition (EMT). HDAC inhibitor SAHA been shown revert EMT in different tumours, including HNC. In study, we investigated cooperative role tyrosine kinase gefitinib both...

Head and Neck cancer (HNC) is a fatal malignancy with poor prognosis. Human Papillomavirus (HPV) infection becoming the prominent cause of HNC in western world, studying molecular mechanisms underlying its action cancers key towards targeted therapy. To replicate, HPV regulates host DNA damage repair (DDR) pathway. SMAD4 also involved regulation DDR machinery likely plays important role maintaining cell viability upon genotoxic stress. In this study, we investigated upregulation to control...

Human Papillomavirus (HPV)-positive Head and Neck (HNC) cancer responds better to radiotherapy platinum-based chemotherapy than HPV-negative HNC, likely due impaired DNA damage repair. Inhibiting PARP1 enhances the effects of radiation in tumours with defective repair, such as HPV-positive cancers. In this study we investigated role HPV upregulation PARP1, determining HNC cell sensitivity both olaparib cisplatin. expression was assessed using TCGA data, lines frozen tumour tissue samples...

Abstract Histone deacetylases (HDACs) catalyze the removal of acetyl molecules from histone and non-histone substrates playing important roles in chromatin remodeling control gene expression. Class I HDAC1 is a critical regulator cell cycle progression, cellular proliferation differentiation during development; it also regulated by many post-translational modifications (PTMs). Herein we characterize new mitosis-specific phosphorylation driven Aurora kinases A B. We show that this affects...

The response to β2-adrenoceptor agonists is reduced in asthmatic airways. This desensitization may be part due inflammatory mediators and involve cysteinyl-leukotrienes (cysteinyl-LTs). Cysteinyl-LTs are pivotal that play important roles the pathophysiology of asthma, allergic rhinitis, other conditions. We tested hypothesis leukotriene D4 (LTD4) allergen challenge cause through activation protein kinase C (PKC). isoproterenol-induced cAMP accumulation was evaluated human airway smooth...

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P63, and in particular the most expressed ΔNp63α isoform, seems to have a critical role outcome of head neck cancer. Many studies been conducted assess possible use p63 as prognostic marker squamous cell carcinoma cancers, but results are still not well defined. Moreover, clear relationship between expression presence high-risk HPV E6 E7 oncoproteins has delineated. Here we describe how is mostly HPV-positive compared HPV-negative cancer lines, with very good correlation mRNA protein levels.

Autophagy is important for the removal, degradation and recycling of damaged organelles, proteins, lipids through degradative action lysosomes. In addition to its catabolic function, autophagy in cancer viral-mediated tumorigenesis, including Human Papillomavirus (HPV) positive cancers. HPV infection a major risk factor subset head neck (HNC), which no targeted therapies are currently available. Herein, we assessed function HPV-positive HNC. We showed that HNC cells presented transcriptional...

Exposure of normal and tumor-derived cells to TGFβ results in different outcomes, depending on the regulation key targets. The CDK inhibitor p27Kip1 is one these targets essential for TGFβ-induced cell cycle arrest. treatment inhibits degradation induces its nuclear translocation, through mechanisms that are still unknown. Recent evidences suggest SUMOylation, a post-translational modification able modulate stability subcellular localization target proteins, critically modifies members...

Functional loss of E-cadherin is frequent during tumor progression and occurs through a variety mechanisms, including proteolytic cleavage. downregulation leads to the conversion more malignant phenotype promoting Epithelial Mesenchymal Transition (EMT). The UBC9/SUMO pathway has been also shown be involved in regulation EMT different cancers. Here we found an increased expression UBC9 Head Neck Cancer (HNC) uncovered role for hampering HPV-mediated cleavage HNC.

Abstract Autophagy is important for removal, degradation and recycling of damaged organelles, proteins, lipids through the degradative action lysosomes. In addition to its catabolic function, autophagy in cancer viral-mediated tumorigenesis, including Human Papillomavirus (HPV) positive cancers. HPV infection a major risk factor subset Head Neck Cancer (HNC), which no targeted therapies are currently available. Herein, we assessed function HPV-positive HNC. We showed that HNC cells presented...

Phospholipase C epsilon (PLCε) is a recently discovered PLC that, in contrast to other PLCs, responds directly inputs from Ras and Rho family small G‐proteins. Using primary astrocytes isolated PLCε‐deficient mouse strain we show that endogenous G‐protein coupled receptors for LPA, S1P thrombin utilize predominantly PLCε inositol phosphate (InsP) DAG formation. LPA‐ S1P‐mediated InsP production was sensitive Pertussis toxin (65±8% 74±9% inhibition respectively) whereas the response reduced...