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Blog of Signaling Pathways

Platelet-derived growth factor BB enhances osteoclast formation and osteoclast precursor cell chemotaxis

1386 views | Nov 05 2017

Li DQ et al. showed that PDGF-BB enhanced RAW264.7 cell migration and gene expression of osteoclastogenic signaling molecules (i.e., nuclear factor of activated T cells 1, dendrocyte-expressed seven transmembrane protein, and B-cell lymphoma 2), and treatment with AG-1295, AG-490, or S3I-201 (a STAT3 inhibitor) reduced this effect. PDGF-BB enhanced osteoclast formation, osteoclast precursor cell chemotaxis, and phosphorylation of STAT3, Akt, and ERK1/2. but AG-1295 and AG-490 reduced this effect. These findings reflect the complexity of PDGF-BB in bone biology. [Read the Full Post]

Regulated intramembrane proteolysis of the AXL receptor kinase generates an intracellular domain that localizes in the nucleus of cancer cells

838 views | Nov 04 2017

Lu Y et al. suggested that AXL can undergo sequential processing mediated by various proteases kept in a homeostatic balance. [Read the Full Post]

Role of protein arginine methyltransferase 5 in inflammation and migration of fibroblast-like synoviocytes in rheumatoid arthritis

600 views | Nov 04 2017

Chen D et al. suggested that targeting PRMT5 to prevent synovial inflammation and destruction might be a promising therapy for RA. [Read the Full Post]

IGF-II-mediated downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α in myoblast cells involves PI3K/Akt/FoxO1 signaling pathway

622 views | Nov 03 2017

Mu X et al. indicated that IGF-II reduces PGC-1α expression in skeletal muscle cells through a mechanism involving PI3K-Akt-FoxO1 but not p38 MAPK or Erk1/2 MAPK pathways. [Read the Full Post]

Hepatocyte growth factor reduces sensitivity to the epidermal growth factor receptor-tyrosine kinase inhibitor, gefitinib, in lung adenocarcinoma cells harboring wild-type EGFR

0 views | Nov 02 2017

Yang H et al. suggested that HGF reduced the gefitinib sensitivity through MET and downstream PI3K and MAPK pathways. [Read the Full Post]

BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity

865 views | Nov 02 2017

Rasmussen RD et al. proposed that GBM cells are addicted to the RS-protective role of the BRCA1-RRM2 axis, targeting of which may represent a novel paradigm for therapeutic intervention in GBM. [Read the Full Post]

Antitumor effect of FGFR inhibitors on a novel cholangiocarcinoma patient derived xenograft mouse model endogenously expressing an FGFR2-CCDC6 fusion protein

0 views | Nov 01 2017

Wang Y et al. provided a strong rationale for the investigation of FGFR inhibitors, particularly BGJ398, as a therapeutic option for cholangiocarcinoma patients harboring FGFR2 fusions. [Read the Full Post]

Anidulafungin-Induced Suicidal Erythrocyte Death

0 views | Nov 01 2017

Anidulafungin triggers hemolysis and eryptosis with cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to Ca2+ entry and activation of p38 kinase. [Read the Full Post]

Inhibition of β-Catenin to Overcome Endocrine Resistance in Tamoxifen-Resistant Breast Cancer Cell Line

0 views | Oct 31 2017

Won HS et al. suggested that beta-catenin plays a role in tamoxifen-resistant breast cancer, and the inhibition of beta-catenin may be a potential target in tamoxifen-resistant breast cancer. [Read the Full Post]

Phosphoinositide 3-Kinase δ Regulates Dectin-2 Signaling and the Generation of Th2 and Th17 Immunity

0 views | Oct 31 2017

Lee MJ, et al. demonstrated that PI3Kδ regulates Dectin-2 signaling and its dendritic cell function. [Read the Full Post]

Coordinate involvement of Nodal-dependent inhibition and Wnt-dependent activation in the maintenance of organizer-specific bmp2b in zebrafish

1111 views | Oct 30 2017

Xue Y et al. suggested that maintenance of organizer-specific bmp2b expression involves opposite and concerted regulation by Nodal and Wnt signaling. [Read the Full Post]

S100B impairs glycolysis via enhanced poly(ADP-ribosyl)ation of glyceraldehyde-3-phosphate dehydrogenase in rodent muscle cells

1218 views | Oct 30 2017

Hosokawa K et al. concluded that S100B as a humoral factor may impair glycolysis in muscle cells independent of insulin action, and the effect may be attributed to the inhibition of GAPDH activity from enhanced poly(ADP-ribosyl)ation of the enzyme. conclude that S100B as a humoral factor may impair glycolysis in muscle cells independent of insulin action, and the effect may be attributed to the inhibition of GAPDH activity from enhanced poly(ADP-ribosyl)ation of the enzyme. [Read the Full Post]

Functional Effects of AKT3 on Aurora Kinase Inhibitor-induced Aneuploidy

0 views | Oct 29 2017

Noguchi K et al. suggested that AKT3 could repress the antiproliferative effects of AURKi, with a novel activity particularly suppressing the aneuploidy induction. [Read the Full Post]

Enhancement of macrophage inflammatory responses by CCL2 is correlated with increased miR-9 expression and downregulation of the ERK1/2 phosphatase Dusp6

680 views | Oct 29 2017

Carson WF 4th et al. indicated that CCL2 supports the classical activation of macrophages, with miR-9 mediated down-regulation of Dusp6 and enhanced ERK-mediated signal transduction possibly mediating this enhanced pro-inflammatory gene expression. [Read the Full Post]

Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations

944 views | Oct 28 2017

Yalon M et al. showed that combination of vorinostat and ABT-888 could potentially prove useful for treatment of cancer with innate resistance to PARPis due to active HRR machinery, while the combination of vorinostat and 6-TG could potentially overcome innate or acquired resistance to PARPis due to secondary or reversal BRCA mutations, to decreased PARP-1 level or to increased expression of multiple drug resistant proteins. [Read the Full Post]

Cancer-associated fibroblasts promote hepatocellular carcinoma metastasis through chemokine-activated hedgehog and TGF-β pathways

1157 views | Oct 28 2017

Liu J et al. found that CAF-secreted CCL2, CCL5, CCL7 and CXCL16 promote HCC metastasis through the coordinate activation of Hh and TGF-β pathways in HCC cells. [Read the Full Post]

Disulfiram overcomes bortezomib and cytarabine resistance in Down-syndrome-associated acute myeloid leukemia cells

692 views | Oct 26 2017

Bista R et al. provided evidence that DSF/Cu2+ overcomes Ara-C and BTZ resistance in cell lines from DS-AMKL patients. A novel mutation underlying BTZ resistance was detected that may identify BTZ-resistant patients, who may not benefit from treatment with CFZ or Ara-C, but may be responsive to DSF/Cu2+. Our findings support the clinical development of DSF/Cu2+ as a less toxic efficacious treatment approach in patients with relapsed/refractory DS-AMKL. [Read the Full Post]

MEK inhibitors block growth of lung tumours with mutations in ataxia-telangiectasia mutated

1145 views | Oct 26 2017

Smida M et al. showed that ATM mutational status in lung cancer is a mechanistic biomarker for MEK inhibitor response, which may improve patient stratification and extend the applicability of these drugs beyond RAS and BRAF mutant tumours. [Read the Full Post]

Impairment of Cargo Transportation Caused by gbf1 Mutation Disrupts Vascular Integrity and Causes Hemorrhage in Zebrafish Embryos

1071 views | Oct 25 2017

Chen J et al. showed that endothelial endoplasmic reticulum stress and subsequent apoptosis induced by gbf1 deficiency may account for the vascular collapse and hemorrhage. [Read the Full Post]

EMT is associated with, but does not drive resistance to ALK inhibitors among EML4-ALK non-small cell lung cancer

0 views | Oct 25 2017

Gower A et al. showed that EMT does not drive resistance to ALK inhibitors and HSP90 inhibition demonstrates more efficacy when further ALK inhibition may not. This study warrants more exploration of HSP90 inhibitors for ALK-positive patients who progress on 1st and 2nd line ALK inhibitor therapy. [Read the Full Post]