Blog of Signaling Pathways

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

996 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

1090 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

589 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

826 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

948 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

586 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

1023 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

935 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]

Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment

1576 views | Oct 24 2017

Katsushima K et al. showed that highlight the importance of the Notch-lncRNA axis in regulating self-renewal of glioma cells and provide a strong rationale for targeting TUG1 as a specific and potent therapeutic approach to eliminate the GSC population. [Read the Full Post]

PI3K Inhibitors Synergize with FGFR Inhibitors to Enhance Antitumor Responses in FGFR2mutant Endometrial Cancers

0 views | Oct 24 2017

Packer L et al. provided evidence that subtherapeutic doses of PI3K inhibitors enhance the efficacy of anti-FGFR therapies, and a combination therapy may represent a superior therapeutic treatment in patients with FGFR2mutant endometrial cancer. [Read the Full Post]

HSPA5 Regulates Ferroptotic Cell Death in Cancer Cells

622 views | Oct 23 2017

Zhu S et al. identified a novel role of HSPA5 in ferroptosis and suggest a potential therapeutic strategy for overcoming gemcitabine resistance. [Read the Full Post]

Chemotherapy-induced Dkk-1 expression by primary human mesenchymal stem cells is p53 dependent

1040 views | Oct 23 2017

Hare I et al. indicated that Dkk-1 has been shown to promote tumor growth in several models of malignancy, suggesting that MSC-derived Dkk-1 could counteract the intent of cytotoxic chemotherapy, and that pharmacologic inhibition of Dkk-1 in patients receiving chemotherapy treatment for certain malignancies may be warranted. [Read the Full Post]

Novel Mechanisms for the Antifibrotic Action of Nintedanib

1270 views | Oct 22 2017

Rangarajan S et al. showed that Nintedanib down-regulated protein and mRNA expression of extracellular matrix (ECM) proteins, fibronectin, and collagen 1a1 while inhibiting transforming growth factor (TGF)-β1-induced myofibroblast differentiation. Nintedanib also induced beclin-1-dependent, ATG7-independent autophagy. Nintedanib's ECM-suppressive actions were not mediated by canonical autophagy. Nintedanib inhibited early events in TGF-β signaling, specifically tyrosine phosphorylation of the type II TGF-β receptor, activation of SMAD3, and p38 mitogen-activated protein kinase. Nintedanib down-regulates ECM production and induces noncanonical autophagy in IPF fibroblasts while inhibiting TGF-β signaling. [Read the Full Post]

ABT-888 and quinacrine induced apoptosis in metastatic breast cancer stem cells by inhibiting base excision repair via adenomatous polyposis coli

1088 views | Oct 22 2017

Siddharth S et al. showed that increased APC physically interacts with PARP-1 and inhibits PARylation causing the non assembly of base excision repair (BER) multiprotein complex, resulting in an irreparable DNA damage and subsequent apoptosis. Knockdown of APC in mBCSCs inhibited DNA damage, increased BER and PARylation, reduces apoptosis while the over-expression of APC in BT20 (APC low expressing) cells reversed the effect. Thus, combination of QC and ABT-888 decreased mBCSCs growth by activating APC and inhibiting BER within the cells. [Read the Full Post]