Blog of Signaling Pathways

BRAF Inhibitors Amplify the Proapoptotic Activity of MEK Inhibitors by Inducing ER Stress in NRAS-Mutant Melanoma

473 views | Nov 29 2018

Niessner H et al. presented herein encourage further advanced in vivo and clinical studies to evaluate MEKi in combination with ER stress inducing BRAFi as a strategy to treat rapidly progressing NRAS-mutant melanoma. [Read the Full Post]

Targeted inhibition of Polo-like kinase 1 by a novel small-molecule inhibitor induces mitotic catastrophe and apoptosis in human bladder cancer cells

468 views | Nov 28 2018

Zhang Z et al. demonstrated of bladder cancer growth inhibition and dissemination using a pharmacological inhibitor of PLK1 provides new opportunities for future therapeutic intervention. [Read the Full Post]

SOCS3 overexpression enhances ADM resistance in bladder cancer T24 cells

1211 views | Nov 28 2018

Li MZ et al. indicated that SOCS3 reduction was associated with bladder cancer sensitivity to ADM. SOCS3 overexpression decreased JAK-STAT3 signaling pathway activity, declined Bcl-2 expression, inhibited cell proliferation, elevated cell apoptosis, and enhanced ADM sensitivity in T24 cells. [Read the Full Post]

Cellular uptake pathways of sepiolite nanofibers and DNA transfection improvement

593 views | Nov 27 2018

Castro-Smirnov FA et al. showed that sepiolite can be spontaneously internalized into mammalian cells through both non-endocytic and endocytic pathways, macropinocytosis being one of the main pathways. Interestingly, exposure of the cells to endocytosis inhibitors, such as chloroquine, two-fold increase the efficiency of sepiolite-mediated gene transfer, in addition to the 100-fold increased resulting from sepiolite sonomechanical treatment. As sepiolite is able to bind various biological molecules, this nanoparticulate silicate could be a good candidate as a nanocarrier for simultaneous vectorization of diverse biological molecules. [Read the Full Post]

Cancer stem cell marker phenotypes are reversible and functionally homogeneous in a preclinical model of pancreatic cancer

0 views | Nov 27 2018

Dosch JS et al. showed that the hierarchical organization of CSCs in human disease is not recapitulated in a commonly used mouse model of pancreatic cancer and therefore provide a new view of the phenotypic and functional heterogeneity of tumor cells. [Read the Full Post]

A sensitive virus yield assay for evaluation of Antivirals against Zika Virus

0 views | Nov 26 2018

Goebel S et al. indicated that due to reproducible assay performance, qPCR associated higher sensitivity and short duration of the assay time, this novel cell based assay will be very useful for confirming the activity of antivirals against ZIKV. [Read the Full Post]

The c.1085A>G Genetic Variant of CSF1R Gene Regulates Tumor Immunity by Altering the Proliferation, Polarization, and Function of Macrophages

425 views | Nov 26 2018

Yeh YM et al. indicated that CSF1R c.1085A>G genetic variant regulates tumor immunity by altering the polarization and function of macrophages. This genetic variant confers the sensitivity to CSF-1R inhibitors, implying as a biomarker in targeting CSF-1R signaling for cancer treatment. [Read the Full Post]

Berberine-sonodynamic therapy induces autophagy and lipid unloading in macrophage

543 views | Nov 25 2018

Kou JY et al. demonstrate that BBR-SDT effectively promotes cholesterol efflux by increasing reactive oxygen species generation, and this subsequently induces autophagy via the PI3K/AKT/mTOR signaling pathway in both 'normal' macrophages and lipid-loaded macrophages (foam cells). Thus, BBR-SDT may be a promising atheroprotective therapy to inhibit the progression of atherosclerosis and should be further studied. [Read the Full Post]

Phosphatidylinositol 3-kinase δ blockade increases genomic instability in B cells

1140 views | Nov 25 2018

Compagno M et al. showed that PI3Kδ or Bruton's tyrosine kinase inhibitors increase genomic instability in normal and neoplastic B cells by an AID-dependent mechanism. This effect should be carefully considered, as such inhibitors can be administered to patients for years. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

0 views | Nov 24 2018

SiRNAs that selectively reduced CSLC only were found to target genes for cholesterol and unsaturated fatty acid synthesis. [Read the Full Post]

RCN1 suppresses ER stress-induced apoptosis via calcium homeostasis and PERK-CHOP signaling

1027 views | Nov 24 2018

Xu S et al. indicated that RCN1, a target of NF-κB, suppresses ER calcium release by binding to IP3R1 and decreases the UPR, thereby inhibiting ER stress-induced apoptosis. [Read the Full Post]

Autophagy Plays an Important Role in Anti-inflammatory Mechanisms Stimulated by Alpha7 Nicotinic Acetylcholine Receptor

610 views | Nov 23 2018

Shao BZ et al. demonstrated for the first time that activating α7nAChR enhances monocyte/microglia autophagy, which suppresses neuroinflammation and thus plays an alleviative role in EAE. [Read the Full Post]

PI3K Catalytic Isoform Alteration Promotes the LIMK1-related Metastasis Through the PAK1 or ROCK1/2 Activation in Cigarette Smoke-exposed Ovarian Cancer Cells.

1328 views | Nov 23 2018

Park GB et al. found that LIMK1 could be a common therapeutic target of ovarian cancer metastasis. [Read the Full Post]

DCLK1 is correlated with MET and ERK5 expression, and associated with prognosis in malignant pleural mesothelioma

553 views | Nov 22 2018

Wang H et al. suggested that DCLK1 is regulated by MET/ERK5 signaling in human mesothelioma, and the MET/ERK5/DCLK1 signaling cascade could be further developed into a promising therapeutic target against mesothelioma. [Read the Full Post]

ABCB1 as predominant resistance mechanism in cells with acquired SNS-032 resistance

0 views | Nov 22 2018

Löschmann N et al. showed that ABCB1 expression represents the primary (sometimes exclusive) resistance mechanism in neuroblastoma cells with acquired resistance to SNS-032. [Read the Full Post]

Host Serine/Threonine Kinases mTOR and Protein Kinase C-α Promote InlB-Mediated Entry of Listeria monocytogenes

5826 views | Nov 21 2018

Bhalla M et al. identified mTOR and PKC-α to be host factors exploited by Listeria to promote infection. PKC-α controls Listeria entry, at least in part, by regulating the actin cytoskeleton downstream of the Met receptor. [Read the Full Post]

ROS-Dependent Activation of Autophagy through the PI3K/Akt/mTOR Pathway Is Induced by Hydroxysafflor Yellow A-Sonodynamic Therapy in THP-1 Macrophages

499 views | Nov 21 2018

Jiang Y et al. demonstrated that HSYA-SDT induces an autophagic response via the PI3K/Akt/mTOR signaling pathway and inhibits inflammation by reactive oxygen species in THP-1 macrophages. [Read the Full Post]

Canonical hedgehog signalling regulates hepatic stellate cell-mediated angiogenesis in liver fibrosis

0 views | Nov 20 2018

Zhang F et al. provided evidence that the canonical hedgehog pathway controlled HSC-mediated liver angiogenesis. Selective inhibition of HSC hedgehog signalling could be a promising therapeutic approach for hepatic fibrosis. [Read the Full Post]

Drug-protein hydrogen bonds govern the inhibition of the ATP hydrolysis of the multidrug transporter P-glycoprotein

0 views | Nov 20 2018

Chufan EE et al. revealed that screening chemical compounds for their ability to inhibit the basal ATP hydrolysis can be a reliable tool to identify modulators with high affinity for P-gp. [Read the Full Post]

Inhibition of HIF-1α by PX-478 suppresses tumor growth of esophageal squamous cell cancer in vitro and in vivo

1913 views | Nov 19 2018

Zhu Y et al. indicated that PX-478 had significant antitumor activity against HIF-1α over-expressing ESCC tumors in vitro and in vivo. These results opened up the possibility of inhibiting HIF-1α for targeted therapy of ESCC. [Read the Full Post]