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Blog of Signaling Pathways

Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma

2249 views | Sep 09 2017

Thompson JM et al. suggested that synthetic lethality between ROCK inhibition and VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC. [Read the Full Post]

BRAF kinase inhibitor exerts anti-tumor activity against breast cancer cells via inhibition of FGFR2

0 views | Sep 08 2017

Zhang ZX et al. indicated that vemurafenib targets the FGFR2-mediated AKT signaling pathway in endothelial cells, leading to the suppression of tumor growth and angiogenesis. [Read the Full Post]

Autophagy induction contributes to GDC-0349 resistance in head and neck squamous cell carcinoma (HNSCC) cells

0 views | Sep 08 2017

Zhou Y et al. provided evidences to support GDC-0349 as a promising anti-HNSCC agent. [Read the Full Post]

Neuronal Soluble Fas Ligand Drives M1-Microglia Polarization after Cerebral Ischemia

0 views | Sep 07 2017

Meng HL et al. involved the activation of JAK2/STAT3 and NF-κB signaling pathways. [Read the Full Post]

Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells.

0 views | Sep 07 2017

Zhang W et al. provided evidence showing that YM155 could act as a small molecule survivin inhibitor on survivin-rich expressed SCC9 cells in culture as well as when grown as tumor in a xenograft model. [Read the Full Post]

Embelin Reduces Systemic Inflammation and Ameliorates Organ Injuries in Septic Rats Through Downregulating STAT3 and NF-κB Pathways

2320 views | Sep 05 2017

Zhou XL et al. indicated that embelin ameliorates sepsis in rats through suppressing STAT3 and NF-κB pathways. [Read the Full Post]

Regulation of TRPM7 Function by IL-6 through the JAK2-STAT3 Signaling Pathway

1316 views | Sep 05 2017

Liu A et al. indicated IL-6 inhibits the inward TRPM7 current via the JAK2-STAT3 signaling pathway. [Read the Full Post]

Role of BmDredd during Apoptosis of Silk Gland in Silkworm, Bombyx mori

1489 views | Sep 04 2017

Chen RT et al. suggested that BmDredd plays a critical role in SG apoptosis. [Read the Full Post]

Calcineurin and GSK-3 inhibition sensitizes T-cell acute lymphoblastic leukemia cells to apoptosis through X-linked inhibitor of apoptosis protein degradation

1076 views | Sep 04 2017

Tosello V et al. showed that dual Cn and GSK-3 inhibitor treatment in vitro and in vivo is effective against available models of T-ALL, indicating an insofar untapped therapeutic opportunity. [Read the Full Post]

The Role of the Active Oxygen Produced from Gp91phox NADPH Oxidase on the Newborn Weight of Mouse Pups

1565 views | Sep 03 2017

Keiichi Hiramoto et al. indicated that gp91phox NADPH oxidase produces ROS during graviditas. The ROS activate NLRP3, and NLRP3 leads to the production of caspase-1, which subsequently increases IL-1, thereby finally inducing IGF-1. Because the newborn weight is determined by IGF-1, gp91phox appears to be important for promoting fetal growth during graviditas. [Read the Full Post]

IGF/STAT3/NANOG/Slug Signaling Axis Simultaneously Controls Epithelial-Mesenchymal Transition and Stemness Maintenance in Colorectal Cancer

1023 views | Sep 01 2017

Yao C et al. defined the crucial functions of IGF/STAT3/NANOG/Slug signaling axis in the progression of CRC by operating EMT and CSCs properties, which make them served as potential therapeutic targets for treatment of CRC. [Read the Full Post]

Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia

3128 views | Sep 01 2017

Simioni C et al. showed that dephosphorylation of pAkt and pS6 showed the cytotoxicity of these compounds. Either single or combined administration of drugs against the different targets displayed inhibition of cellular viability associated with a concentration-dependent induction of apoptosis, cell cycle arrest in G0/G1 phase and autophagy, having the combined treatments a significant synergistic cytotoxic effect. Co-targeting NUP214-ABL1 fusion gene and PI3K/Akt/mTOR signaling pathway could represent a new and effective pharmacological strategy to improve the outcome in NUP214-ABL1 positive T-ALL. [Read the Full Post]

Anticancer effects of the engineered stem cells transduced with therapeutic genes via a selective tumor tropism caused by vascular endothelial growth factor toward HeLa cervical cancer cells

1413 views | Aug 31 2017

Kim HS et al. showed that GESTECs transduced with CD gene and IFN-β may provide a potential of a novel gene therapy for anticervical cancer treatments via their selective tumor tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTECs. [Read the Full Post]

Oncogene swap as a novel mechanism of acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor in lung cancer

1886 views | Aug 31 2017

Mizuuchi H et al. analyzed multiple lesions from a patient who died of acquired resistance to gefitinib, then found a clinical example of an oncogene swap in which the EGFR mutation was lost and a MET gene copy was gained. In conclusion, an "oncogene swap" from EGFR to MET is a novel resistant mechanism to the EGFR-TKI. This novel mechanism should be considered in order to avoid futile inhibition of the original oncogene. [Read the Full Post]

Neuronal Soluble Fas Ligand Drives M1-Microglia Polarization after Cerebral Ischemia

0 views | Aug 30 2017

Meng HL et al. involved the activation of JAK2/STAT3 and NF-κB signaling pathways. [Read the Full Post]

Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells

0 views | Aug 30 2017

Zhang W et al. suggested that survivin could be further developed as a potential therapeutic agent for the treatment of survivin-rich expressed OSCC. [Read the Full Post]

Inhibition of PRMT5 suppresses osteoclast differentiation and partially protects against ovariectomy-induced bone loss through downregulation of CXCL10 and RSAD2

821 views | Aug 29 2017

Dong Y et al. found that PRMT5 is an activator of osteoclast differentiation and inhibition of PRMT5 partially suppressed osteoclastogenesis through downregulation of CXCL10 and RSAD2. [Read the Full Post]

Rhein Inhibits AlkB Repair Enzymes and Sensitizes Cells to Methylated DNA Damage

1232 views | Aug 28 2017

Li Q et al. revealed that rhein binds to AlkB repair enzymes in vitro and promotes thermal stability in vivo In addition, we have determined a new structural complex of rhein bound to AlkB, which shows that rhein binds to a different part of the active site in AlkB than it binds to in fat mass and obesity-associated protein (FTO). [Read the Full Post]

Leptin-STAT3-G9a Signaling Promotes Obesity-Mediated Breast Cancer Progression

997 views | Aug 28 2017

Chang CC et al. showed how targeting STAT3-G9a signaling regulates CSC plasticity during obesity-related breast cancer progression, suggesting a novel therapeutic paradigm to suppress CSC pools and limit breast malignancy. [Read the Full Post]

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay

1962 views | Aug 27 2017

Laporte AN et al. report use of the proximity ligation assay to confirm the oncogenic association of SS18-SSX with its co-factor TLE1 in multiple human synovial sarcoma cell lines and in surgically-excised human tumor tissue. SS18-SSX/TLE1 interactions are disrupted by class I HDAC inhibitors and novel small molecule inhibitors. This assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known. [Read the Full Post]