HOX family transcription factors: Related signaling pathways and post-translational modifications in cancer.
Abstract HOX family transcription factors belong to a highly conserved subgroup of the homeobox superfamily that determines cellular fates in embryonic morphogenesis and the maintenance of adult tissue architecture. HOX family transcription factors play key roles in numerous cellular processes including cell growth, differentiation, apoptosis, motility, and angiogenesis. As tumor promoters or suppressors HOX family members have been reported to be closely related with a variety of cancers. They closely regulate tumor initiation and growth, invasion and metastasis, angiogenesis, anti-cancer drug resistance and stem...
Source: Cellular Signalling - November 13, 2019 Category: Cytology Authors: Yu M, Zhan J, Zhang H Tags: Cell Signal Source Type: research

A super-enhancer controls TGF- β signaling in pancreatic cancer through downregulation of TGFBR2.
A super-enhancer controls TGF- β signaling in pancreatic cancer through downregulation of TGFBR2. Cell Signal. 2019 Nov 12;:109470 Authors: Zhu X, Zhang T, Zhang Y, Chen H, Shen J, Jin X, Wei J, Zhang E, Xiao M, Fan Y, Mao R, Zhou G Abstract Pancreatic cancer is one of the most lethal malignant tumors due to a late diagnosis and highly invasion and metastasis. Transforming growth factor-β (TGF-β) signaling plays a vital role in the progression of pancreatic cancer. The delicate activity of TGF-β signaling is particular important for the development of aggression and metastasis whic...
Source: Cellular Signalling - November 12, 2019 Category: Cytology Authors: Zhu X, Zhang T, Zhang Y, Chen H, Shen J, Jin X, Wei J, Zhang E, Xiao M, Fan Y, Mao R, Zhou G Tags: Cell Signal Source Type: research

Interleukin-10 induces senescence of activated hepatic stellate cells via STAT3-p53 pathway to attenuate liver fibrosis.
Abstract Hepatic fibrosis is a wound healing process which results in deposition of excessive abnormal extracellular matrix (ECM) in response to various liver injuries. Activated hepatic stellate cells (HSCs) are the major sources of ECM and induction of senescence of activated HSCs is an attractive therapeutic strategy for liver fibrosis. Our previous studies have shown that interleukin-10 (IL-10) attenuates the carbon tetrachloride (CCL4) - and porcine serum-induced liver fibrosis in rats. However, little is known about the mechanisms of IL-10 regulating the senescence of activated HSCs. The aim of this study is...
Source: Cellular Signalling - November 12, 2019 Category: Cytology Authors: Huang YH, Chen MH, Guo QL, Chen ZX, Chen QD, Wang XZ Tags: Cell Signal Source Type: research

Gastric cancer proliferation and invasion is reduced by macrocalyxin C via activation of the miR-212-3p/Sox6 Pathway.
Abstract Gastric cancer is a malignancy of very poor prognosis and survival rates. Macrocalyxin C is a Chinese herb-derived diterpenoid compound that has been postulated to possess anti-cancer characteristics. Gastic cell viability and stage of cell cycle were assessed using CCK8 assay and flow cytometry, respectively. Cell migration and invation were assessed using the wound healing and Transwell assays. Rate of apoptosis was determined via AV/PI-staining. Athymic nude mice xenograft models were used to evaluate the in vivo efficacy of macrocalyxin C. Western blot, luciferase experiments, cell transfection and re...
Source: Cellular Signalling - November 11, 2019 Category: Cytology Authors: Dang Y, Liu T, Yan J, Reinhardt JD, Yin C, Ye F, Zhang G Tags: Cell Signal Source Type: research

The PI3K/Akt/mTOR pathway in polycystic kidney disease: A complex interaction with polycystins and primary cilium.
Abstract Over-activation of the PI3K/Akt/mTOR network is a well-known pathogenic event that leads to hyper-proliferation. Pharmacological targeting of this pathway has been developed for the treatment of multiple diseases, including cancer. In polycystic kidney disease (PKD), the mTOR cascade promotes cyst growth by boosting proliferation, size and metabolism of kidney tubule epithelial cells. Therefore, mTOR inhibition has been tested in pre-clinical and clinical studies, but only the former showed positive results. This review reports recent discoveries describing the activity and molecular mechanisms of mTOR ac...
Source: Cellular Signalling - November 9, 2019 Category: Cytology Authors: Margaria JP, Campa CC, De Santis MC, Hirsch E, Franco I Tags: Cell Signal Source Type: research

Activation of CRHR1 contributes to cerebral endothelial barrier impairment via cPLA2 phosphorylation in experimental ischemic stroke.
Abstract The activation of corticotrophin-releasing hormone receptor (CRHR) 1 is implicated in neuronal injury in experimental stroke. However, little is known about the relationship between CRHR1 activation and brain endothelial barrier impairment after ischemia and reperfusion (I/R). Recently we have demonstrated that the activation of extracellular signal-regulated kinase (Erk) 1/2 as well as p38 is required for hydrogen peroxide (H2O2)-increased cytosolic phospholipase A2 (cPLA2) phosphorylation in bEnd3 cells. Using this in vitro ischemic-like model, we found that both blockade and interference of CRHR1 inhib...
Source: Cellular Signalling - November 9, 2019 Category: Cytology Authors: Cao C, Zhou J, Wu X, Qian Y, Hong Y, Mu J, Jin L, Zhu C, Li S Tags: Cell Signal Source Type: research

microRNA-485-5p inhibits the progression of hepatocellular carcinoma through blocking the WBP2/Wnt signaling pathway.
Abstract microRNA-485-5p (miR-485-5p) has been shown to act as a tumor-suppressor gene in some cancers, such as ovarian epithelial tumors and oral tongue squamous cell carcinoma. However, with regard to the anti-tumor role of miR-485-5p in hepatocellular carcinoma (HCC), evidence is unexpectedly limited. In the present study, we investigated the expression and the role of miR-485-5p in the progression of HCC. Microarray analysis revealed that miR-485-5p was downregulated and WBP2 was upregulated in HCC, which was consistent with RT-qPCR and immunohistochemistry assays in the HCC tissues we collected. A negative co...
Source: Cellular Signalling - November 6, 2019 Category: Cytology Authors: Gao J, Dai C, Yu X, Yin XB, Zhou F Tags: Cell Signal Source Type: research

Regulation of cell cycle by MDM2 in prostate cancer cells through Aurora Kinase-B and p21WAF1/CIP1 mediated pathways.
Abstract Overexpression of MDM2 oncoprotein has been detected in a large number of diverse human malignancies and has been shown to play both p53-dependent and p53-independent roles in oncogenesis. Our study was designed to explore the impact of MDM2 overexpression on the levels of various cell cycle regulatory proteins including Aurora kinase-B (AURK-B), CDC25C and CDK1, which are known to promote tumor progression and increase metastatic potential. Our data from human cell cycle RT2 prifiler PCR array experiments revealed significant changes in the expression profile of genes that are involved in different phase...
Source: Cellular Signalling - November 6, 2019 Category: Cytology Authors: Kanagasabai T, Venkatesan T, Natarajan U, Alobid S, Alhazzani K, Algahtani M, Rathinavelu A Tags: Cell Signal Source Type: research

Effect of FSH on E2/GPR30-mediated mouse oocyte maturation in vitro.
In conclusion, our study reveals that FSH induced estrogen production in mouse COCs through aromatase, and that aromatase/GPR30/ERK1/2 signaling is involved in FSH-induced cumulus expansion. PMID: 31704004 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - November 5, 2019 Category: Cytology Authors: Zhao H, Ge J, Wei J, Liu J, Liu C, Ma C, Zhao X, Wei Q, Ma B Tags: Cell Signal Source Type: research

Corrigendum to "Two non-coding RNAs, MicroRNA-101 and HOTTIP contribute cartilage integrity by epigenetic and homeotic regulation of integrin- α1" [Cell Signal. 25(12) (2013) 2878-2887].
Corrigendum to "Two non-coding RNAs, MicroRNA-101 and HOTTIP contribute cartilage integrity by epigenetic and homeotic regulation of integrin-α1" [Cell Signal. 25(12) (2013) 2878-2887]. Cell Signal. 2019 Nov 04;:109455 Authors: Kim D, Song J, Han J, Kim Y, Chun CH, Jin EJ PMID: 31699459 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - November 4, 2019 Category: Cytology Authors: Kim D, Song J, Han J, Kim Y, Chun CH, Jin EJ Tags: Cell Signal Source Type: research

Integrin alpha 7 correlates with poor clinical outcomes, and it regulates cell proliferation, apoptosis and stemness via PTK2-PI3K-Akt signaling pathway in hepatocellular carcinoma.
This study aimed to evaluate the correlation of integrin alpha 7 (ITGA7) with clinical outcomes and its effect on cell activities as well as stemness in hepatocellular carcinoma (HCC). HCC tumor tissues and paired adjacent tissues from 90 HCC patients were obtained and ITGA7 expression was detected using immunohistochemistry assay. Cellular experiments were conducted to examine the effect of ITGA7 on cell activities, astemness via ITGA7 ShRNA transfection, and compensation experiments were further performed to test whether ITGA7 functioned via regulating PTK2-PI3K-AKT signaling pathway. ITGA7 was overexpressed in tumor tis...
Source: Cellular Signalling - November 4, 2019 Category: Cytology Authors: Ge JC, Wang YX, Chen ZB, Chen DF Tags: Cell Signal Source Type: research

Epithelial cell plasticity defines heterogeneity in lung cancer.
Abstract Lung cancer is the leading cause of cancer death for both men and women and accounts for almost 18.4% of all deaths due to cancer worldwide, with the global incidence increasing by approximately 0.5% per year. Lung cancer is regarded as a devastating type of cancer owing to its high prevalence, reduction in the health-related quality of life, frequently delayed diagnosis, low response rate, high toxicity, and resistance to available therapeutic options. The highly heterogeneous nature of this cancer with a proximal-to-distal distribution throughout the respiratory tract dramatically affects its diagnostic...
Source: Cellular Signalling - November 3, 2019 Category: Cytology Authors: Sarode P, Mansouri S, Karger A, Schaefer MB, Grimminger F, Seeger W, Savai R Tags: Cell Signal Source Type: research

Pirfenidone inhibits motility of NSCLC cells by interfering with the urokinase system.
a M Abstract Pirfenidone (PFD) is an orally available synthetic drug which has been approved for the treatment of idiopathic pulmonary fibrosis. In addition to its anti-fibrotic properties, PFD also exerts anti-tumor effects in cancer models by inducing alterations in the tumor microenvironment. Here, we demonstrate that PFD reduces proliferation, 2D- and 3D-migration as well as colony formation of the non-small-cell lung carcinoma (NSCLC) cells. On a molecular level, we show that PFD on the one hand interacts with plasminogen activator inhibitor-1 (PAI-1; Kd of 46.2 ± 11.3 nM) and affe...
Source: Cellular Signalling - November 3, 2019 Category: Cytology Authors: Krämer M, Markart P, Drakopanagiotakis F, Mamazhakypov A, Schaefer L, Didiasova M, Wygrecka M Tags: Cell Signal Source Type: research

A novel long non-coding RNA LINC00355 promotes proliferation of lung adenocarcinoma cells by down-regulating miR-195 and up-regulating the expression of CCNE1.
Abstract Lung adenocarcinoma is the most common subtype of non-small-cell lung cancer affecting people all over the globe. Recent studies have indicated that long non-coding RNAs (lncRNAs) possess the ability to regulate gene expression. Initially, we uncovered increased LINC00355 expressions in lung adenocarcinoma tissues and cells. Functionally, our findings demonstrated that LINC00355 silencing suppressed the proliferation in vitro and in vivo. In addition, we found that LINC00355 negatively regulated miR-195 in lung adenocarcinoma cells. Simultaneously, silencing LINC00355 by shRNA resulted in suppressed proli...
Source: Cellular Signalling - November 2, 2019 Category: Cytology Authors: Liang Y, Rong X, Luo Y, Li P, Han Q, Wei L, Wang E Tags: Cell Signal Source Type: research

Differentiation of human neuroblastoma cell line IMR-32 by sildenafil and its newly discovered analogue IS00384.
This study highlights the role of phosphodiesterases-5 in neurodifferentiation and use of sildenafil and IS00384 as small molecule tools to study the process of cellular differentiation. PMID: 31689507 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - November 2, 2019 Category: Cytology Authors: Dar MI, Jan S, Lakshma Reddy G, Wani R, Mudassir S, Dar MJ, Sawant SD, Vishwakarma RA, Syed SH Tags: Cell Signal Source Type: research

Native and iron-saturated bovine lactoferrin differently hinder migration in a model of human glioblastoma by reverting epithelial-to-mesenchymal transition-like process and inhibiting interleukin-6/STAT3 axis.
Abstract Glioblastoma, the most lethal form of brain cancer, is characterized by fast growth, migration and invasion of the surrounding parenchyma, with epithelial-to-mesenchymal transition (EMT)-like process being mostly responsible for tumour spreading and dissemination. A number of actors, including cadherins, vimentin, transcriptional factors such as SNAIL, play critical roles in the EMT process. The interleukin (IL)-6/STAT3 axis has been related to enhanced glioblastoma's migration and invasion abilities as well. Here, we present data on the differential effects of native and iron-saturated bovine lactoferrin...
Source: Cellular Signalling - October 31, 2019 Category: Cytology Authors: Cutone A, Colella B, Pagliaro A, Rosa L, Lepanto MS, Bonaccorsi di Patti MC, Valenti P, Di Bartolomeo S, Musci G Tags: Cell Signal Source Type: research

TCDD-mediated suppression of na ïve human B cell IgM secretion involves aryl hydrocarbon receptor-mediated reduction in STAT3 serine 727 phosphorylation and is restored by Interferon-γ.
TCDD-mediated suppression of naïve human B cell IgM secretion involves aryl hydrocarbon receptor-mediated reduction in STAT3 serine 727 phosphorylation and is restored by Interferon-γ. Cell Signal. 2019 Oct 31;:109447 Authors: Blevins LK, Zhou J, Crawford R, Kaminski NE Abstract 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant formed as a byproduct in organic synthesis and burning of organic materials. TCDD has potent immunotoxic effects in B lymphocytes resulting in decreased cellular activation and suppressed IgM secretion following activation with CD40...
Source: Cellular Signalling - October 31, 2019 Category: Cytology Authors: Blevins LK, Zhou J, Crawford R, Kaminski NE Tags: Cell Signal Source Type: research

Sustained GRK2-dependent CREB activation is essential for α2-adrenergic receptor-induced PC12 neuronal differentiation.
Sustained GRK2-dependent CREB activation is essential for α2-adrenergic receptor-induced PC12 neuronal differentiation. Cell Signal. 2019 Oct 31;:109446 Authors: Karkoulias G, McCrink KA, Maning J, Pollard CM, Desimine VL, Patsouras N, Psallidopoulos M, Taraviras S, Lymperopoulos A, Flordellis C Abstract Many aspects of neuronal development, such as neuronal survival and differentiation, are regulated by the transcription factor cAMP-response element-binding protein (CREB). We have previously reported that α2-adrenergic receptors (ARs), members of the G protein-coupled receptor (GPCR) supe...
Source: Cellular Signalling - October 31, 2019 Category: Cytology Authors: Karkoulias G, McCrink KA, Maning J, Pollard CM, Desimine VL, Patsouras N, Psallidopoulos M, Taraviras S, Lymperopoulos A, Flordellis C Tags: Cell Signal Source Type: research

Osteogenic gene markers are epigenetically reprogrammed during contractile-to-calcifying vascular smooth muscle cell phenotype transition.
Abstract The understanding of vascular calcification-based mechanism is an urgent pending task in vascular biology and this prompted us to better address this issue by investigating whether DNA methylation mechanism might drive osteogenic marker genes modulation in primary human vascular smooth muscle cells (VSMCs) responding to calcium and phosphate levels overload up to 72 hours. Firstly, our data shows this calcifying process recapitulates the molecular repertory of osteogenic biomarkers and specifically requiring RUNX2, Osterix and ALP, BSP genes activations along 72 hours in vitro, and this beha...
Source: Cellular Signalling - October 30, 2019 Category: Cytology Authors: da Silva RA, da S Feltran G, da C Fernandes CJ, Zambuzzi WF Tags: Cell Signal Source Type: research

Gankyrin promotes osteosarcoma tumorigenesis by forming a positive feedback loop with YAP.
CONCLUSIONS: Our results identify that gankyrin acts as an oncogene in OS by forming a positive feedback loop with YAP, and disrupting the gankyrin-YAP regulation may be beneficial for controlling OS tumorigenesis. PMID: 31678253 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - October 30, 2019 Category: Cytology Authors: Cheng L, Wu B, Zhang L, Bian E, An R, Yu S, Liu W, Xiong Z Tags: Cell Signal Source Type: research

SCFFBXO28-mediated self-ubiquitination of FBXO28 promotes its degradation.
Abstract The F-box protein is the substrate recognition subunit of SCF (SKP1/CUL1/F-box) E3 ubiquitin ligase complex, a multicomponent RING-type E3 ligase involved in the regulation of numerous cellular processes by targeting critical regulatory proteins for ubiquitination. However, whether and how F-box proteins are regulated is largely unknown. Here we report that FBXO28, a poorly characterized F-box protein, is a novel substrate of SCF E3 ligase. Pharmaceutical or genetic inhibition of neddylation pathway that is required for the activation of SCF stabilizes FBXO28 and prolongs its half-life. Meanwhile, FBXO28 ...
Source: Cellular Signalling - October 30, 2019 Category: Cytology Authors: Cai L, Liu L, Li L, Jia L Tags: Cell Signal Source Type: research

Muscarinic receptor stimulation induces TASK1 channel endocytosis through a PKC-Pyk2-Src pathway in PC12 cells.
In this study, proximity ligation assay (PLA) and other molecular biological approaches were used to elucidate the details of this muscarinic signaling in PC12 cells. When green fluorescent protein (GFP)-TASK1 was expressed, the majority of GFP-TASK1 was located at the cell periphery. However, the simultaneous expression of GFP-TASK1 and PKCα, but not PKCδ, led to GFP-TASK1 internalization. Muscarinic receptor stimulation resulted in transient co-localization of Pyk2 and Src at the cell periphery, and expression of kinase dead (KD) Pyk2 and Src, but not Pyk2 and KD Src, resulted in GFP-TASK1 internalization. PL...
Source: Cellular Signalling - October 29, 2019 Category: Cytology Authors: Matsuoka H, Harada K, Mashima K, Inoue M Tags: Cell Signal Source Type: research

MLL2 promotes cancer cell lymph node metastasis by interacting with RelA and facilitating STC1 transcription.
Abstract Esophageal squamous cell carcinoma (ESCC) presents with lymph node metastasis in the early stages, limiting the opportunities for curative local resection, including endoscopic submucosal dissection (ESD). ESD is regarded as the standard treatment for early-stage ESCCs. However, radical surgery is recommended when lymph node metastasis risk exists. More efforts are needed to find the markers for early prediction and clarify the molecular mechanism underlying the pathogenesis of lymph node metastasis. Recently, aberrant regulation of gene expression by histone methylation modifiers has emerged as an import...
Source: Cellular Signalling - October 29, 2019 Category: Cytology Authors: Li H, Li Q, Lian J, Chu Y, Fang K, Xu A, Chen T, Xu M Tags: Cell Signal Source Type: research

LncRNA NEAT1 promotes docetaxel resistance in prostate cancer by regulating ACSL4 via sponging miR-34a-5p and miR-204-5p.
Abstract Docetaxel resistance remains one of the main problems in clinical treatment of metastatic prostate cancer (PCa). Previous studies identified differently expressed lncRNAs in docetaxel-resistant PCa cell lines, while the potential mechanisms were still unknown. In the present study, we found NEAT1 was expressed at high levels in docetaxel-resistant PCa clinical samples and related cell lines. When knockdown NEAT1, cell proliferation and invasion in docetaxel-resistant PCa cells in vitro and in vivo were downregulated. Our further researches explained that NEAT1 exerts oncogenic function in PCa by competiti...
Source: Cellular Signalling - October 28, 2019 Category: Cytology Authors: Jiang X, Guo S, Zhang Y, Zhao Y, Li X, Jia Y, Xu Y, Ma B Tags: Cell Signal Source Type: research

Niche origin of mesenchymal stem cells derived microvesicles determines opposing effects on NSCLC: primary versus metastatic.
In conclusion, the systemic nature of MVs marks them as attractive therapeutic markers/targets and we propose that identification of specific cargoes/signals that differentiate between MSCs MVs of primary and metastatic niches may introduce fresh therapeutic approaches. PMID: 31672605 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - October 28, 2019 Category: Cytology Authors: Attar-Schneider O, Dabbah M, Drucker L, Gottfried M Tags: Cell Signal Source Type: research

1-O-alkyl glycerophosphate-induced CD36 expression drives oxidative stress in microglial cells.
In this study, we investigated the role of AGP in microglial activation and illustrated the underlying molecular mechanism. We found that AGP treatment increased the production of intracellular reactive oxygen species and induced PPARγ activation in microglial cells. Interestingly, AGP also up-regulated the expression levels of the cluster of differentiation 36 (CD36) scavenger receptor, a high-affinity receptor for oxidized low-density lipoproteins. The findings suggest that AGP induces PPARγ activation, enhances CD36 expression and increases the production of intracellular reactive oxygen species (ROS) in mic...
Source: Cellular Signalling - October 27, 2019 Category: Cytology Authors: Tsukahara T Tags: Cell Signal Source Type: research

Active mixture of serum-circulating small molecules selectively inhibits proliferation and triggers apoptosis in cancer cells via induction of ER stress.
In this study, we show that the AM elicits gene expression changes characteristic of endoplasmic reticulum (ER) stress in HeLa, MCF-7, PC-3 and Caco-2 cancer cells, but not in primary human renal epithelial cells. The activation of the ER stress pathway was confirmed by the upregulation of ATF3, ATF4, CHAC1, DDIT3 and GDF15 proteins. Mechanistically, our investigation revealed that eIF2α, PERK and IRE1α are phosphorylated upon treatment with the AM, linking the induction of ER stress to the antiproliferative and proapoptotic effects of the AM previously demonstrated. Inhibition of ER stress in combination with ...
Source: Cellular Signalling - October 26, 2019 Category: Cytology Authors: Scheffer D, Kulcsár G, Nagyéri G, Kiss-Merki M, Rékási Z, Maloy M, Czömpöly T Tags: Cell Signal Source Type: research

Corrigendum to "Hsp90/Cdc37 assembly modulates TGF β receptor-II to act as a profibrotic regulator of TGFβ signaling during cardiac hypertrophy" [Cell. Signal. 27 (12) (2015) 2410-2424].
Corrigendum to "Hsp90/Cdc37 assembly modulates TGFβ receptor-II to act as a profibrotic regulator of TGFβ signaling during cardiac hypertrophy" [Cell. Signal. 27 (12) (2015) 2410-2424]. Cell Signal. 2019 Oct 23;:109437 Authors: Datta R, Bansal T, Rana S, Datta K, Chattopadhyay S, Chawla-Sarkar M, Sarkar S PMID: 31668398 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - October 23, 2019 Category: Cytology Authors: Datta R, Bansal T, Rana S, Datta K, Chattopadhyay S, Chawla-Sarkar M, Sarkar S Tags: Cell Signal Source Type: research

Bone marrow-derived mesenchymal stem cells repair severe acute pancreatitis by secreting miR-181a-5p to target PTEN/Akt/TGF- β1 signaling.
CONCLUSION: BMSCs alleviate SAP and reduce inflammatory responses and apoptosis by secreting miR-181a-5p to target PTEN/Akt/TGF-β1 signaling. Hence, BMSCs-miR-181a-5p could serve as potential therapeutic target for SAP. PMID: 31654716 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - October 22, 2019 Category: Cytology Authors: Li HY, He HC, Song JF, Du YF, Guan M, Wu CY Tags: Cell Signal Source Type: research

Identification of Nogo-B as a new molecular target of peroxisome proliferator-activated receptor gamma.
In this study, we found PPARγ activation by rosiglitazone or dephosphorylation increased Nogo-B expression at mRNA and protein levels in HepG2 cells and mouse primary hepatocytes. Furthermore, we identified a PPARγ response element (PPRE) in Nogo-B promoter and found PPARγ enhanced Nogo-B transcription in a PPRE-dependent manner. ChIP assay further confirms rosiglitazone enhanced the binding of PPARγ to Nogo-B promoter. Using a liver specific PPARγ deficient mice, we determined the critical role of PPARγ expression in regulating hepatic Nogo-B expression. Increased glucose and palmitate ...
Source: Cellular Signalling - October 22, 2019 Category: Cytology Authors: Yu M, Zhang S, Guo F, Yang X, Li Q, Wei Z, Han J, Duan Y, Chen Y Tags: Cell Signal Source Type: research

Involvement of hyaluronan and CD44 in cancer and viral infections.
Abstract Hyaluronan and its major receptor CD44 are ubiquitously distributed. They have important structural as well as signaling roles, regulating tissue homeostasis, and their expression levels are tightly regulated. In addition to signaling initiated by the interaction of the intracellular domain of CD44 with cytoplasmic signaling molecules, CD44 has important roles as a co-receptor for different types of receptors of growth factors and cytokines. Dysregulation of hyaluronan-CD44 interactions is seen in diseases, such as inflammation and cancer. In the present communication, we discuss the mechanism of hyaluron...
Source: Cellular Signalling - October 22, 2019 Category: Cytology Authors: Heldin P, Kolliopoulos C, Lin CY, Heldin CH Tags: Cell Signal Source Type: research

Vav1 mutations: what makes them oncogenic?
Abstract Vav1 is physiologically active as a GDP/GTP nucleotide exchange factor (GEF) in the hematopoietic system. Its wild-type form was recently implicated in mammalian malignancies of hematologic and non-hematologic tissue origins. Moreover, it was recently identified as a mutated gene in human cancers of various origins. In this review we focus on the functional activities of several of the Vav1 mutants analyzed for their tumorigenic properties. We also discuss the relationship of the tested biochemical properties of Vav1 mutants, E59 K, D517E and L801 P, to their computer-based predicted propert...
Source: Cellular Signalling - October 22, 2019 Category: Cytology Authors: Farago M, Yarnitzky T, Shalom B, Katzav S Tags: Cell Signal Source Type: research

Betacellulin enhances ovarian cancer cell migration by up-regulating Connexin43 via MEK-ERK signaling.
Abstract Epithelial ovarian cancer is the fifth common cause of cancer death in women and the most lethal gynecological malignancies. Our previous studies have shown that up-regulation of Connexin43, a gap-junction subunit crucial for cell-cell communication, enhances ovarian cancer cell migration. Betacellulin is a member of the epidermal growth factor (EGF) family which can bind to multiple EGF family receptors. Overexpression of betacellulin is found in a variety of cancers and is associated with reduced survival. However, the specific roles and molecular mechanisms of betacellulin in ovarian cancer progression...
Source: Cellular Signalling - October 22, 2019 Category: Cytology Authors: Zhao J, Klausen C, Yi Y, Cheng JC, Chang HM, Leung PCK Tags: Cell Signal Source Type: research

NLS-RAR α contributes to differentiation block and increased leukemogenic potential in vivo.
This study was designed to evaluate the value of NLS-RARα in the early diagnosis of APL. To investigate the potential functional role of NLS-RARα in leukemogenesis, HL-60 and U937 cell lines were transfected with NLS-RARα lentivirus and negative control (LV-NC). The results showed that the induced expression of NLS-RARα down-regulated expressions of CD11b, CD11c, and CD14 compared to the LV-NC group induced by 1α, 25-dihydroxyvitamin D3(1,25(OH)2D3). This suggested that NLS-RARα overexpression inhibited granulocytic and monocytic differentiation of myeloid leukemia cells. In addition, Wr...
Source: Cellular Signalling - October 22, 2019 Category: Cytology Authors: Xiong L, Zhong L, Yu L, Dan W, Ye J, Li J, Liu D, Yuan Z, Yao J, Zhong P, Liu J, Liu B Tags: Cell Signal Source Type: research

Long non-coding RNA KCNQ1OT1/microRNA-204-5p/LGALS3 axis regulates myocardial ischemia/reperfusion injury in mice.
In conclusion, KCNQ1OT1 binds to miR-204-5p to exacerbate myocardial IR injury in mice through the up-regulation of LGALS3, providing a novel insight for myocardial IR injury treatment. PMID: 31644943 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - October 20, 2019 Category: Cytology Authors: Rong J, Pan H, He J, Zhang Y, Hu Y, Wang C, Fu Q, Fan W, Zou Q, Zhang L, Tang Y, Peng X, Wang P, Xiang Y, Peng J, Liu Z, Zheng Z Tags: Cell Signal Source Type: research

Midkine promotes articular chondrocyte proliferation through the MK-LRP1-nucleolin signaling pathway.
Abstract Osteoarthritis (OA) is the most common disease of joint tissues; unfortunately, there are currently no curative therapies available for OA. Chondrocytes, the only cell type residing in cartilage, secrete many types of collagen (the mainly one is type II collagen) and aggrecan, which are the main components of the cartilage matrix. Chondrocyte apoptosis can lead to OA degenerative progression. We previously indicated that recombinant human midkine (rhMK), as a chondrocyte growth factor has a significant reparative effect on cartilage injury animal models. However, the molecular mechanism of this restorativ...
Source: Cellular Signalling - October 19, 2019 Category: Cytology Authors: Deng Q, Yu X, Deng S, Ye H, Zhang Y, Han W, Li J, Yu Y Tags: Cell Signal Source Type: research

Novel compounds for the modulation of mTOR and autophagy to treat neurodegenerative diseases.
rri J Abstract Most neurodegenerative diseases show a disruption of autophagic function and display abnormal accumulation of toxic protein aggregates that promotes cellular stress and death. Therefore, induction of autophagy has been proposed as a reasonable strategy to help neurons clear abnormal protein aggregates and survive. The kinase mammalian target of rapamycin (mTOR) is a major regulator of the autophagic process and is regulated by starvation, growth factors, and cellular stressors. The phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway, which promotes cellular survival, is the main modulat...
Source: Cellular Signalling - October 19, 2019 Category: Cytology Authors: Heras-Sandoval D, Pérez-Rojas JM, Pedraza-Chaverri J Tags: Cell Signal Source Type: research

Tula proteins as signaling regulators.
TULA PROTEINS AS SIGNALING REGULATORS. Cell Signal. 2019 Oct 19;:109424 Authors: Tsygankov AY Abstract Two members of the UBASH3/STS/TULA family exhibit a unique protein domain structure, which includes a histidine phosphatase domain, and play a key role in regulating cellular signaling. UBASH3A/STS-2/TULA is mostly a lymphoid protein, while UBASH3B/STS-1/TULA-2 is expressed ubiquitously. Dephosphorylation of tyrosine-phosphorylated proteins by TULA-2 and, probably to a lesser extent, by TULA critically contribute to the molecular basis of their regulatory effect. The notable differences between the e...
Source: Cellular Signalling - October 19, 2019 Category: Cytology Authors: Tsygankov AY Tags: Cell Signal Source Type: research

Upregulation of microRNA-141 contributes to suppressing epithelial-mesenchymal transition and lymph node metastasis in laryngeal cancer through HOXC6-dependent TGF- β signaling pathway.
In this study, we aim to explore the roles of microRNA-141 (miR-141), Homeobox C6 (HOXC6) and TGF-β signaling pathway in epithelial-mesenchymal transition (EMT) and lymph node metastasis in laryngeal cancer. Initially, we identified differentially expressed genes in laryngeal cancer, among which HOXC6 was identified. Then the target miRNA of HOXC6 was predicted and verified. Next, expression of miR-141, HOXC6, TGF-β1, Smad3, Vimentin and Snail in cancer tissues was detected. Then, AMC-HN-8 cells were transfected with miR-141 mimic, miR-141 inhibitor and HOXC6-siRNA to investigate specific role of miR-141, HOXC6 a...
Source: Cellular Signalling - October 16, 2019 Category: Cytology Authors: Chen L, Sun DZ, Fu YG, Yang PZ, Lv HQ, Gao Y, Zhang XY Tags: Cell Signal Source Type: research

Selective recruitment of Nck and Syk contribute to distinct leukocyte immune-type receptor-initiated target interactions.
Abstract The ability of phagocytes to recognize, immobilize, and engulf extracellular targets are fundamental immune cell processes that allow for the destruction of a variety of microbial intruders. The phagocytic process depends on the signalling activity of immunoregulatory receptor-types that initiate dynamic changes in plasma membrane architecture required to accommodate the internalization of large particulate targets. To better understand fundamental molecular mechanisms responsible for facilitating phagocytic receptor-mediated regulation of cytoskeletal networks, our research has focused on investigating r...
Source: Cellular Signalling - October 15, 2019 Category: Cytology Authors: Lillico DME, Pemberton JG, Niemand R, Stafford JL Tags: Cell Signal Source Type: research

Knockdown of DEAD-box RNA helicase DDX5 selectively attenuates serine 311 phosphorylation of NF- κB p65 subunit and expression level of anti-apoptotic factor Bcl-2.
Knockdown of DEAD-box RNA helicase DDX5 selectively attenuates serine 311 phosphorylation of NF-κB p65 subunit and expression level of anti-apoptotic factor Bcl-2. Cell Signal. 2019 Oct 15;:109428 Authors: Tanaka K, Tanaka T, Nakano T, Hozumi Y, Yanagida M, Araki Y, Iwazaki K, Takagi M, Goto K Abstract NF-κB plays a key role in the transcriptional regulation of genes involved in immunity, inflammation, cell proliferation, and oncogenesis. The NF-κB activation process includes nuclear translocation, followed by association with basal transcription machinery. These steps are tightly re...
Source: Cellular Signalling - October 15, 2019 Category: Cytology Authors: Tanaka K, Tanaka T, Nakano T, Hozumi Y, Yanagida M, Araki Y, Iwazaki K, Takagi M, Goto K Tags: Cell Signal Source Type: research

Retinoic acid signalling adjusts tight junction permeability in response to air-liquid interface conditions.
Abstract The pulmonary epithelium separates the gaseous intraluminal space of the airways and the aqueous interstitium. This compartimentalization is required for appropriate lung function, it is established during perinatal periods and can be disturbed in lung edema. Herein we elaborated the impact of the air-liquid interface (ALI) on the function of the pulmonary epithelium. We used NCI-H441 epithelia as a well-established and characterized model of distal airway epithelia, which were cultivated either at ALI or (at submerged conditions) at liquid-liquid interface conditions (LLI). Our study revealed that parace...
Source: Cellular Signalling - September 16, 2019 Category: Cytology Authors: Lochbaum R, Schilpp C, Nonnenmacher L, Frick M, Dietl P, Wittekindt OH Tags: Cell Signal Source Type: research

Alzheimer's disease pathogenesis: The role of disturbed sleep in attenuated brain plasticity and neurodegenerative processes.
Abstract Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairments. The classical symptoms of the disease include gradual deterioration of memory and language. Epidemiological studies indicate that around 25-40% of AD patients have sleep-wake cycle disturbances. Importantly, a series of studies suggested that the relationship between AD and sleep disturbance may be complex and bidirectional. Indeed, accumulation of the extracellular neuronal protein amyloid-beta (Aβ) leads to altered sleep-wake behavior in both mice and humans. At the same time, disturbances of the normal...
Source: Cellular Signalling - September 16, 2019 Category: Cytology Authors: Havekes R, Heckman PRA, Wams EJ, Stasiukonyte N, Meerlo P, Eisel ULM Tags: Cell Signal Source Type: research

AGR3 promotes the stemness of colorectal cancer via modulating Wnt/ β-catenin signalling.
AGR3 promotes the stemness of colorectal cancer via modulating Wnt/β-catenin signalling. Cell Signal. 2019 Sep 14;:109419 Authors: Chi J, Zhang H, Hu J, Song Y, Li J, Wang L, Wang Z Abstract Cancer cells with stem cell properties have been acknowledged to be responsible for cancer initiation and progression. Wnt/β-catenin signalling is a major signal pathway promoting the stemness of cancer cells. Anterior gradient 3 (AGR3), a member of the protein disulfide isomerase (PDI) family, was found to be overexpressed in several cancers. However, the roles and mechanisms of AGR3 in colorectal cance...
Source: Cellular Signalling - September 14, 2019 Category: Cytology Authors: Chi J, Zhang H, Hu J, Song Y, Li J, Wang L, Wang Z Tags: Cell Signal Source Type: research

Receptor-specific regulation of atrial GIRK channel activity by different Ca2+-dependent PKC isoforms.
Abstract G Protein-activated K+ channels (GIRK) channels are inhibited by depletion of PtdIns(4,5)P2(PIP2), and/or channel phosphorylation by proteinkinase C (PKC). By using FRET-based biosensors, expressed in HEK293 cells or in atrial myocytes, we quantified receptor-specific Gq-coupled receptor (GqPCR) signalling on the level of phospholipase C (PLC) activation by monitoring PIP2-depletion and diacylglycerol (DAG) formation. Simultaneous voltage-clamp experiments on GIRK channel activity were performed as a functional readout for Gq-coupled α1B- and ET-receptor-induced signalling. GqPCR-induced fast inhibi...
Source: Cellular Signalling - September 13, 2019 Category: Cytology Authors: Niemeyer A, Rinne A, Kienitz MC Tags: Cell Signal Source Type: research

Redox signaling in ischemic postconditioning protection involves PKC ε and Erk1/2 pathways and converges indirectly in Nrf2 activation.
Redox signaling in ischemic postconditioning protection involves PKCε and Erk1/2 pathways and converges indirectly in Nrf2 activation. Cell Signal. 2019 Sep 13;:109417 Authors: Díaz-Ruíz JL, Macías-López A, Alcalá-Vargas F, Guevara-Chávez JG, Mejía-Uribe A, Silva-Palacios A, Zúñiga-Muñoz A, Zazueta C, Buelna-Chontal M Abstract Ischemic-postconditioning (iPostC) exerts cardioprotection by preserving redox homeostasis in the reperfused heart. This protective effect has been associated with the activation of endogenous antioxid...
Source: Cellular Signalling - September 13, 2019 Category: Cytology Authors: Díaz-Ruíz JL, Macías-López A, Alcalá-Vargas F, Guevara-Chávez JG, Mejía-Uribe A, Silva-Palacios A, Zúñiga-Muñoz A, Zazueta C, Buelna-Chontal M Tags: Cell Signal Source Type: research

Signaling alterations caused by drugs and autophagy.
Abstract Autophagy is an evolutionary conserved process that recycles cellular materials in times of nutrient restriction to maintain viability. In cancer therapeutics, the role of autophagy in response to multi-kinase inhibitors, alone or when combined with histone deacetylase (HDAC) inhibitors acts, generally, to facilitate the killing of tumor cells. Furthermore, the formation of autophagosomes and subsequent degradation of their contents can reduce the expression of HDAC proteins themselves as well as of other signaling regulatory molecules such as protein chaperones and mutated RAS proteins. Reduced levels of...
Source: Cellular Signalling - September 11, 2019 Category: Cytology Authors: Dent P, Booth L, Poklepovic A, Hancock JF Tags: Cell Signal Source Type: research

KDM3A inhibition modulates macrophage polarization to aggravate post-MI injuries and accelerates adverse ventricular remodeling via an IRF4 signaling pathway.
In this study, we aimed to demonstrate whether KDM3A could regulate the polarization of macrophages to affect the inflammatory response after myocardial infarction and whether targeting KDM3A could influence the prognosis of myocardial infarction and adverse LV remodeling. To explore the biological function of KDM3A and the underlying mechanisms, the loss of function experiments were designed in vitro and vivo. we analyzed the function of macrophages by a phagocytosis and migration assay and explored the polarization of macrophages. The expression of macrophage inflammation-related genes in the acute inflammatory phase and...
Source: Cellular Signalling - September 9, 2019 Category: Cytology Authors: Liu X, Chen J, Zhang B, Liu G, Zhao H, Hu Q Tags: Cell Signal Source Type: research

Inhibition of vascular smooth muscle cell calcification by vasorin through interference with TGF β1 signaling.
In conclusion, vasorin, which suppresses TGFβ1 signaling and protects against osteo-/chondrogenic transdifferentiation and calcification of VSMCs, is reduced by pro-calcifying conditions. Thus, vasorin is a novel key regulator of VSMC calcification and may represent a potential therapeutic target for vascular calcification during CKD. PMID: 31505229 [PubMed - as supplied by publisher] (Source: Cellular Signalling)
Source: Cellular Signalling - September 7, 2019 Category: Cytology Authors: Luong TTD, Estepa M, Boehme B, Pieske B, Lang F, Eckardt KU, Voelkl J, Alesutan I Tags: Cell Signal Source Type: research

STAT3-CyPA signaling pathway in endothelial cell apoptosis.
Abstract Cyclophilin A (CyPA), which is encoded by PPIA, is a ubiquitously expressed intracellular protein and is secreted in response to inflammatory stimuli. CyPA stimulates proinflammatory and apoptosis signaling pathways in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), promotes VSMC migration and proliferation, EC adhesion molecules expression, and inflammatory cell chemotaxis and apoptosis. Therefore, we sought to study the transcriptional regulation of CyPA, we hypothesized that transcription factor STAT3 regulated CyPA expression and activated vascular ECs in vitro in a CyPA-dependent ma...
Source: Cellular Signalling - September 5, 2019 Category: Cytology Authors: Xie Y, Li X, Ge J Tags: Cell Signal Source Type: research