Blog of Signaling Pathways

Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma

502 views | Mar 25 2018

Xu L et al. showed a significant over-expression of EGFR (66.67%) and IGF1R (80.0%) in ACC. Besides, the co-overexpression of EGFR and IGF1R was seen in 8/15 ACCs, as compared with ACAs (P<0.05). Erlotinib and NVP-AEW541 significantly inhibited cell viability and induced apoptosis by blocking phosphorylation of MEK/ERK and AKT, respectively. Meanwhile, we found that single inhibition of IGF1R induced compensatory activation of MEK/ERK, leading to sustained activation of mTOR, which represent as aggregation of EGFR and IGF1R downstream components. More importantly, the combination of Erlotinib and NVP-AEW541 enhances anti-tumour efficacy compared to treatment with either agent alone or to untreated control in vitro and vivo. [Read the Full Post]

Downregulation of B-myb promotes senescence via the ROS-mediated p53/p21 pathway, in vascular endothelial cells

1233 views | Mar 24 2018

Zhou Z et al. suggested that B-myb may be a novel candidate for regulating cell senescence to protect against endothelial senescence-related cardiovascular diseases. [Read the Full Post]

Nanoformulation of Olaparib Amplifies PARP Inhibition and Sensitizes PTEN/TP53-Deficient Prostate Cancer to Radiation

1112 views | Mar 24 2018

van de Ven AL et al. suggested that NanoOlaparib may be a promising new strategy for enhancing the radiosensitivity of radiation-resistant tumors lacking BRCAmutations, such as those with PTEN and TP53 deletions. [Read the Full Post]

Anti-leukaemic activity of the TYK2 selective inhibitor NDI-031301 in T-cell acute lymphoblastic leukaemia

1533 views | Mar 23 2018

Akahane K et al. supported selective inhibition of TYK2 as a promising potential therapeutic strategy for T-ALL. [Read the Full Post]

Regulation of glutamate transporter trafficking by Nedd4-2 in a Parkinson's disease model

0 views | Mar 23 2018

Zhang Y et al. indicated that Nedd4-2 may serve as a potential therapeutic target for the treatment of PD. [Read the Full Post]

Plumbagin Protects Mice from Lethal Sepsis by Modulating Immunometabolism Upstream of PKM2

523 views | Mar 22 2018

Zhang Z et al. identified a new approach for inhibiting the NOX4/PKM2-dependent immunometabolism pathway in the treatment of sepsis and inflammatory diseases. [Read the Full Post]

Advanced Glycation End-Products Induce Apoptosis of Vascular Smooth Muscle Cells: A Mechanism for Vascular Calcification

634 views | Mar 22 2018

Koike S et al. demonstrated that NAD(P)H oxidase-derived oxidative stress are involved in AGEs-induced apoptosis of VSMCs. These findings might be important to understand the pathogenesis of vascular calcification in diabetes and CKD. [Read the Full Post]

Mutant p53 in concert with an interleukin-27 receptor alpha deficiency causes spontaneous liver inflammation, fibrosis, and steatosis in mice

0 views | Mar 21 2018

Dibra D et al. found that he combination of mutant p53 and IL27RA(-/-) causes spontaneous liver inflammation, steatosis, and fibrosis in vivo, whereas either gene alone in vivo has no effects on the liver. [Read the Full Post]

Sensitivity of Human Intrahepatic Cholangiocarcinoma Subtypes to Chemotherapeutics and Molecular Targeted Agents: A Study on Primary Cell Cultures

600 views | Mar 21 2018

Fraveto A et al. identified a dual PI3-kinase/mTOR inhibitor that both in vitro and in vivo, exerts dramatic antiproliferative effects against both mucin- and mixed-IHCCA. [Read the Full Post]

MST2 phosphorylation at serine 385 in mitosis inhibits its tumor suppressing activity

849 views | Mar 20 2018

Chen X et al. revealed a novel layer of regulation for MST2 in mitosis and its role in tumorigenesis. [Read the Full Post]

CCND1 mutations increase protein stability and promote ibrutinib resistance in mantle cell lymphoma

822 views | Mar 20 2018

Mohanty A et al. uncover a new mechanism that is critical for the regulation of CCND1 protein levels, and is directly relevant to primary ibrutinib resistance in MCL. [Read the Full Post]

Oncogenic epithelial cell-derived exosomes containing Rac1 and PAK2 induce angiogenesis in recipient endothelial cells

599 views | Mar 19 2018

Gopal SK et al. demonstrated for the first time that oncogenic cells undergoing EMT can communicate with endothelial cells via exosomes, and establish exosomal Rac1/PAK2 as angiogenic promoters that may function from early stages of the metastatic cascade. [Read the Full Post]

Nevospheres from neurocutaneous melanocytosis cells show reduced viability when treated with specific inhibitors of NRAS signaling pathway

524 views | Mar 19 2018

Basu D et al. indicated NRAS mutated cells derived from clinical NCM samples are capable of continuous growth as spheroid colonies in vitro and retain their genetic identity. Drugs targeting the NRAS signaling pathway reduce in vitro viability of NCM cells. NCM lesional spheroids represent a new and reliable experimental model of NCM for use in drug testing and mechanistic studies. [Read the Full Post]

Prolactin signaling through focal adhesion complexes is amplified by stiff extracellular matrices in breast cancer cells

846 views | Mar 18 2018

Barcus CE et al. suggested that PRL signaling to FAK and SFKs may be useful targets in clinical aggressive ERα+ breast carcinomas. [Read the Full Post]

METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion

0 views | Mar 18 2018

Zhang Z et al. identified METTL13 as a tumor suppressor and might provide promising approaches for bladder cancer treatment and prevention. [Read the Full Post]

Hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) mediates radiation-induced invasiveness through the SDF-1α/CXCR4 pathway in non-small cell lung carcinoma cells

533 views | Mar 17 2018

Gu Q et al. found the underlying mechanisms of the irradiation-enhanced invasiveness of NSCLC cells. [Read the Full Post]

Relative cytotoxic potencies and cell death mechanisms of α1 -adrenoceptor antagonists in prostate cancer cell lines

0 views | Mar 17 2018

Forbes A et al. demonstrated cytotoxic actions on both castration-resistant PC-3 and androgen-sensitive LNCap prostate cancer cells. [Read the Full Post]

X66, a novel N-terminal heat shock protein 90 inhibitor, exerts antitumor effects without induction of heat shock response.

759 views | Mar 16 2018

Zhao Z et al. found that the HSP90 inhibitory action and the potent antitumor activity, with the anti-HSR action, promise X66 a novel HSP90-targeted agent, which merits further research and development. [Read the Full Post]

Epothilone B induces apoptosis and enhances apoptotic effects of ABT-737 on human cancer cells via PI3K/AKT/mTOR pathway

0 views | Mar 16 2018

Li YL et al. indicated that ABT-737 may be a pertinent sensitizer to epothilone B, and the strategy of combining epothilone B with ABT-737 appears to be an attractive option for overcoming the resistance and neurotoxicity of epothilone B. [Read the Full Post]

NF-YA promotes invasion and angiogenesis by upregulating EZH2-STAT3 signaling in human melanoma cells

1242 views | Mar 15 2018

Xu Z et al. indicated that overexpression of NF-YA contributes to tumor angiogenesis through EZH2-STAT3 signaling in human melanoma cells, highlighting NF-YA as a potential therapeutic target in human melanoma. [Read the Full Post]