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Blog of Signaling Pathways

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

2161 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.

425 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

1245 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

2155 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

887 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.

779 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

1554 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]

Computational Modeling of PI3K/AKT and MAPK Signaling Pathways in Melanoma Cancer

0 views | Jun 19 2017

Pappalardo F et al. showed a computational model able to simulate the main biochemical and metabolic interactions in the PI3K/AKT and MAPK pathways potentially involved in melanoma development. [Read the Full Post]

A novel multi-CDK inhibitor P1446A-05 restricts melanoma growth and produces synergistic effects in combination with MAPK pathway inhibitors

363 views | Jun 19 2017

Eliades P et al. founf that targeting cell cycle and transcriptional CDKs with a small molecule multi-CDK inhibitor is a viable approach for developing novel anti-melanoma therapeutics. [Read the Full Post]

Histone Deacetylase Inhibitor RGFP109 Overcomes Temozolomide Resistance by Blocking NF-κB-Dependent Transcription in Glioblastoma Cell Lines

2570 views | Jun 18 2017

Li ZY et al. showed that RGFP109, an HDAC inhibitor, in combination with TMZ may be a therapeutic candidate for patients with temozolomide-resistant GBM. [Read the Full Post]

PARP Inhibitor Activity Correlates with SLFN11 Expression and Demonstrates Synergy with Temozolomide in Small Cell Lung Cancer

851 views | Jun 18 2017

Lok BH et al. found that SLFN11 is a relevant predictive biomarker of sensitivity to PARP inhibitor monotherapy in SCLC and we identify combinatorial therapy with TMZ as a particularly promising therapeutic strategy that warrants further clinical investigation. [Read the Full Post]

Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function

841 views | Jun 17 2017

Ballandras-Colas A et al. revealed a novel octameric integrase structure for betaretroviral intasome function. [Read the Full Post]

Exploiting Temporal Collateral Sensitivity in Tumor Clonal Evolution.

1151 views | Jun 17 2017

Zhao B, et al. identified new strategies to treat dynamic tumor vulnerabilities. [Read the Full Post]

Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer

2161 views | Jun 16 2017

Liu B et al. concluded that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer. [Read the Full Post]

Functionalized gold nanoparticles improve afatinib delivery into cancer cells

1967 views | Jun 16 2017

Coelho SC et al. found that PEGAuNPs with afatinib is a promising antitumor delivery system for cancer therapy as it improves drug efficacy, allowing a reduction in drug dose used and minimizing possible toxicity-related side effects. [Read the Full Post]

Inhibition of acquired-resistance hepatocellular carcinoma cell growth by combining sorafenib with phosphoinositide 3-kinase and rat sarcoma inhibitor

734 views | Jun 15 2017

Wu CH et al. found that both inhibitors of PI3K/mTOR and RAS/ERK signaling are potentially effective antihepatocellular carcinoma drugs especially in treating sorafenib-resistant hepatocellular carcinoma. [Read the Full Post]

A role of KIT receptor signaling for proliferation and differentiation of rat stem Leydig cells in vitro

1916 views | Jun 15 2017

Liu S et al. found KITL is a growth factor that regulates the development of the stem Leydig cell. [Read the Full Post]

Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling

4572 views | Jun 14 2017

Tsioumpekou M et al. found that PDGF-BB-induced Erk5 activation involves parallel stimulatory and inhibitory pathways and promotes Smad1/5/8 signaling. [Read the Full Post]

Analysis of Endogenous Protein Interactions of Polycomb Group of Proteins in Mouse Embryonic Stem Cells.

1877 views | Jun 14 2017

Morey L et al. described several methods to study Polycomb architecture, and identification of novel interactors in both pluripotent and differentiating mouse embryonic stem cells. [Read the Full Post]