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Blog of Signaling Pathways

Phosphorylation of Astrin Regulates Its Kinetochore Function

0 views | Jul 01 2017

Chung HJ et al. revealed a regulatory circuit for protein targeting to KTs that controls the KT composition change of stable spindle attachment and chromosome [Read the Full Post]

Glucose Metabolism and AMPK Signaling Regulate Dopaminergic Cell Death Induced by Gene (α-Synuclein)-Environment (Paraquat) Interactions

854 views | Jun 30 2017

Anandhan A et al. demonstrated that glucose metabolism and AMPK regulate dopaminergic cell death induced by gene (α-synuclein)-environment (PQ) interactions. [Read the Full Post]

New insights into estrogenic regulation of O6-methylguanine DNA-methyltransferase (MGMT) in human breast cancer cells: Co-degradation of ER-α and MGMT proteins by fulvestrant or O6-benzylguanine indicates fresh avenues for therapy

678 views | Jun 29 2017

Paranjpe A et al. concluded that MGMT and ER-α proteins exist as a complex and are co-targeted for ubiquitin-conjugation and subsequent proteasomal degradation. The findings offer a clear rationale for combining alkylating agents with endocrine therapy. [Read the Full Post]

miR-17-5p down-regulation contributes to erlotinib resistance in non-small cell lung cancer cells

1973 views | Jun 29 2017

Zhang W et al. indicated that miR-17-5p down-regulation contributes to erlotinib resistance of NSCLC by modulating its target genes such as EZH1 and plasma miR-17-5p might be a potential biomarker of erlotinib response in NSCLC patients [Read the Full Post]

Impact of CTLA-4 blockade in conjunction with metronomic chemotherapy on preclinical breast cancer growth

1309 views | Jun 28 2017

Parra K et al. proved Sequential therapy of anti-CTLA-4 followed by gemcitabine is effective in chemotherapy-naive tumours, although tumour relapses can occur, in some cases accompanied by the development of spontaneous metastases. [Read the Full Post]

Amplification of EGFR Wild-Type Alleles in Non-Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors

2349 views | Jun 27 2017

Nukaga S et al. provided evidence of wild-type allele-mediated resistance, a novel concept of acquired resistance in response to mutation-selective inhibitor therapy in cancer treatment. [Read the Full Post]

Phospho-Akt overexpression is prognostic and can be used to tailor the synergistic interaction of Akt inhibitors with gemcitabine in pancreatic cancer

1745 views | Jun 27 2017

Massihnia D et al. found that inhibition of Glut1 might overcome resistance to these therapies and warrants further studies. [Read the Full Post]

Inhibition of Bcl-2 potentiates AZD-2014-induced anti-head and neck squamous cell carcinoma cell activity

0 views | Jun 26 2017

Li Y et al. suggested that AZD-2014 could be further tested as a valuable anti-HNSCC agent, either alone or in combination with Bcl-2 inhibitors. [Read the Full Post]

The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells.

1667 views | Jun 26 2017

Nunn AD et al. demonstrated the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome. [Read the Full Post]

Effects of inhibiting PI3K-Akt-mTOR pathway on lipid metabolism homeostasis in goose primary hepatocytes

1822 views | Jun 25 2017

Liu DD et al. suggested that the reduction of lipids accumulation induced-by inhibiting PI3K-Akt-mTOR pathway was closely linked to the decrease of lipogenesis, the increase of fatty acids oxidation, and the increase of VLDL assembly and secretion in goose hepatocytes. [Read the Full Post]

BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells

2651 views | Jun 25 2017

The immunoblot analysis showed that BEZ235 treatment decreased pAKT, pmTOR and pERK whereas AZD2014 decreased only pmTOR. [Read the Full Post]

Bifunctional alkylating agent-mediated MGMT-DNA cross-linking and its proteolytic cleavage in 16HBE cells

0 views | Jun 24 2017

Cheng J et al. demonstrated that MGMT might turn into a DNA damage promoter by forming DPC when exposed to HN2. Proteolysis, especially DVC1, plays a crucial role in mDPC repair. [Read the Full Post]

Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents

0 views | Jun 24 2017

Zhu J et al. showed that modifications beyond just increasing the lipophilicity of this class of Pgp inhibitors are beneficial to the activity. [Read the Full Post]

A PGC1α-mediated transcriptional axis suppresses melanoma metastasis

2243 views | Jun 23 2017

Luo C et al. revealed that PGC1α maintains mitochondrial energetic metabolism and suppresses metastasis through direct regulation of parallel acting transcriptional programs. [Read the Full Post]

Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability.

435 views | Jun 23 2017

Pattabiraman DR et al. provides proof-of-principle for inducing an MET as differentiation therapy for TICs and uncovers a role for PKA in enforcing and maintaining the epithelial state. [Read the Full Post]

Structural basis of Smoothened regulation by its extracellular domains

1299 views | Jun 22 2017

Byrne EF et al. clarified the structural mechanism by which the activity of a GPCR is controlled by ligand-regulated interactions between its extracellular and transmembrane domains. [Read the Full Post]

Cdk5 is required for the neuroprotective effect of transforming growth factor-β1 against cerebral ischemia-reperfusion

2219 views | Jun 21 2017

Zhao W et al. concluded that Cdk5 contributes to the neuroprotective function of TGF- β1 via ERK1/2 signaling. [Read the Full Post]

Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism

934 views | Jun 21 2017

Yang W, et al. used the ACAT inhibitor avasimibe, which was previously tested in clinical trials for treating atherosclerosis and showed a good human safety profile, to treat melanoma in mice and observed a good antitumour effect. [Read the Full Post]

Hypoxia-induced vasculogenic mimicry formation in human colorectal cancer cells: Involvement of HIF-1a, Claudin-4, and E-cadherin and Vimentin.

802 views | Jun 20 2017

Li W et al. revealed a regulatory role for HIF-1α in VM and suggests that targeting either HIF-1α or EMT may be a valuable strategy for the elimination of CRC metastasis. [Read the Full Post]

Acquired Resistance to the Hsp90 Inhibitor, Ganetespib, in KRAS-Mutant NSCLC Is Mediated via Reactivation of the ERK-p90RSK-mTOR Signaling Network

1592 views | Jun 20 2017

Chatterjee S et al. offered a way forward for Hsp90 inhibitors through the rational design of Hsp90 inhibitor combinations that may prevent and/or overcome resistance to Hsp90 inhibitors, providing an effective therapeutic strategy for KRAS-mutant NSCLC. [Read the Full Post]