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Blog of Signaling Pathways

Tumor-secreted anterior gradient-2 binds to VEGF and FGF2 and enhances their activities by promoting their homodimerization.

853 views | Oct 18 2018

Guo H et al. proposed that the secreted AGR2 is a blockable molecular target, which acts as a chaperon-like enhancer to VEGF and FGF2. [Read the Full Post]

PFK15, a Small Molecule Inhibitor of PFKFB3, Induces Cell Cycle Arrest, Apoptosis and Inhibits Invasion in Gastric Cancer

517 views | Oct 17 2018

Zhu W et al. indicated that PFK15 is a promising anticancer drug for treating gastric cancer. [Read the Full Post]

The selective MEK1 inhibitor Selumetinib enhances the antitumor activity of everolimus against renal cell carcinoma in vitro and in vivo

521 views | Oct 17 2018

Zou Y et al. provided a sound evidence that combination of everolimus and Selumetinib is a potential dual-targeted strategy for renal cell carcinoma. [Read the Full Post]

Inhibition of 6-phosphofructo-2-kinase suppresses fibroblast-like synoviocytes-mediated synovial inflammation and joint destruction in rheumatoid arthritis

447 views | Oct 16 2018

Zou Y et al. showed that elevated PFKFB3 expression might contribute to synovial inflammation and aggressive behaviours of RA FLSs, suggesting a novel strategy of targeting PFKFB3 to prevent synovial inflammation and joint destruction in RA. [Read the Full Post]

Blockage of glycolysis by targeting PFKFB3 suppresses tumor growth and metastasis in head and neck squamous cell carcinoma

442 views | Oct 16 2018

Li HM et al. indicated the pharmacological inhibition of PFKFB3 via PFK15 suppressed tumor growth and alleviated metastasis in HNSCC, offering a promising strategy for cancer therapy. [Read the Full Post]

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

703 views | Oct 15 2018

Goebel S et al. showed 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]

Retinoic acid and TGF-β signalling cooperate to overcome MYCN-induced retinoid resistance

1905 views | Oct 15 2018

Duffy DJ et al. provided a powerful precision oncology tool for identifying the driving signalling networks for malignancies not primarily driven by somatic mutations, such as paediatric cancers. By applying global omics approaches to the signalling networks regulating neuroblastoma differentiation and stemness, we have determined the pathways involved in the MYCN-mediated retinoid resistance, with TGF-β signalling being a key regulator. These findings revealed a number of combination treatments likely to improve clinical response to retinoid therapy, including co-treatment with retinoids and KGN, which may prove valuable in the treatment of high-risk MYCN-amplified neuroblastoma. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 views | Oct 14 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Acquired resistance to combination treatment through loss of synergy with MEK and PI3K inhibitors in colorectal cancer

0 views | Oct 14 2018

Bhattacharya B et al. highlight that AQR to combination treatment may develop through alternative mechanisms to those of single agent treatment, including a change in drug interaction. [Read the Full Post]

Romidepsin induces G2/M phase arrest via Erk/cdc25C/cdc2/cyclinB pathway and apoptosis induction through JNK/c-Jun/caspase3 pathway in hepatocellular carcinoma cells

899 views | Oct 13 2018

Sun WJ et al. offered proof-of-concept for use of Romidepsin as a novel class of chemotherapy in the treatment of HCC. [Read the Full Post]

Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet

441 views | Oct 13 2018

Luo F et al. suggested that atorvastatin/metformin combination therapy may achieve additional anti-atherosclerotic benefits likely through increasing cholesterol efflux in macrophages. [Read the Full Post]

Resistance to RET-Inhibition in RET-Rearranged NSCLC Is Mediated By Reactivation of RAS/MAPK Signaling

1701 views | Oct 12 2018

Nelson-Taylor SK et al. demonstrated that resistance to ponatinib in RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms that result in restored RAS/MAPK activation. [Read the Full Post]

Epigenetic repression of miR-375 is the dominant mechanism for constitutive activation of the PDPK1/RPS6KA3 signalling axis in multiple myeloma.

924 views | Oct 12 2018

Tatekawa S et al. showed the universal involvement of overlapping epigenetic dysregulation for abnormal miR-375 repression in MM, which is likely to contribute to myelomagenesis and to subsequent myeloma progression by activating oncogenic signalling pathways. [Read the Full Post]

Activation of Wnt/β-catenin signalling is required for TGF-β/Smad2/3 signalling during myofibroblast proliferation

780 views | Oct 12 2018

Xu L et al. found that a major outcome of this study is improved insight into the mechanisms by which epithelial and mesenchymal cells activated by TGFβ1-smad2/3 signalling through Wnt/β-catenin contribute to lung fibrosis. [Read the Full Post]

Tumor Necrosis Factor Inhibits Spread of Hepatitis C Virus Among Liver Cells, Independent From Interferons

863 views | Oct 10 2018

Laidlaw SM et al. found TNF to have antiviral effects independently of, as well as in combination with, IFNs. TNF inhibits HCV infection despite increased HCV envelope glycoprotein-mediated infection of liver cells. These findings contradict those from other studies, which have reported that TNF blocks signal transduction in response to IFNs. The destructive inflammatory effects of TNF must be considered along with its antiviral effects. [Read the Full Post]

Targeting Hsp90 with FS-108 circumvents gefitinib resistance in EGFR mutant non-small cell lung cancer cells

523 views | Oct 10 2018

Wang YQ et al. indicated that FS-108 is a powerful agent that impacts the survival of gefitinib-resistant cells in vitro and in vivo through targeting Hsp90. [Read the Full Post]

A multi-targeted liquid chromatography-mass spectrometry screening procedure for the detection in human urine of drugs non-prohibited in sport commonly used by the athletes

704 views | Oct 09 2018

Mazzarino M et al. indicated this work presents an analytical method for the simultaneous analysis in human urine of 38 pharmacologically active compounds (19 benzodiazepine-like substances, 7 selective serotonin reuptake inhibitors, 4 azole antifungal drugs, 5 inhibitors of the phosphodiesterases type 4 and 3 inhibitors of the phosphodiesterase type 5) by liquid-chromatography coupled with tandem mass spectrometry. [Read the Full Post]

PTC725, an NS4B-Targeting Compound, Inhibits a Hepatitis C Virus Genotype 3 Replicon, as Predicted by Genome Sequence Analysis and Determined Experimentally

0 views | Oct 09 2018

Graci JD et al. identified previously unreported amino acid substitutions selected by PTC725 treatment which further demonstrate that these compounds target the NS4B first transmembrane region. [Read the Full Post]

Cyclic tensile strain promotes the osteogenic differentiation of a bone marrow stromal cell and vascular endothelial cell co-culture system

886 views | Oct 08 2018

Jiang Y et al. demonstrated that cyclic tensile strain promotes osteogenic differentiation in BMSC/VEC co-culture systems, possibly via a VEC-mediated paracrine effect of VEGF on BMSCs. [Read the Full Post]

The phosphodiesterase 4 inhibitor roflumilast augments the Th17-promoting capability of dendritic cells by enhancing IL-23 production, and impairs their T cell stimulatory activity due to elevated IL-10

540 views | Oct 08 2018

Bros M et al. suggested that PDE4 inhibitors aside from their broad overall anti-inflammatory effects may enhance the Th17-polarizing capacity in DCs as an unwanted side effect. [Read the Full Post]