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Blog of Signaling Pathways

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

1328 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]

Liraglutide attenuates the osteoblastic differentiation of MC3T3‑E1 cells by modulating AMPK/mTOR signaling

2189 views | Aug 27 2017

Hu XK et al. study demonstrate that liraglutide attenuates osteoblastic differentiation of MC3T3‑E1 cells via modulation of AMPK/mTOR signaling. The present study revealed a novel function of liraglutide, which contributes to the understanding of its pharmacological and physiological effects in clinical settings. [Read the Full Post]

miR-18a promotes cell proliferation of esophageal squamous cell carcinoma cells by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis

0 views | Aug 25 2017

Zhang W et al. demonstrated the upregulation of miR-18a promoted cell proliferation by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis, suggesting that small molecule inhibitors of AKT-mTOR signaling are potential agents for the treatment of ESCC patients with upregulation of miR-17-92 cluster. [Read the Full Post]

Visfatin attenuates the ox-LDL-induced senescence of endothelial progenitor cells by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway

0 views | Aug 25 2017

Ming GF et al. suggested that the treatment of EPCs with visfatin markedly attenuates the ox-LDL-induced senescence of EPCs by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway. [Read the Full Post]

Brain-Penetrating Histone Deacetylase Inhibitor RG2833 Reduces the Viability of Human Malignant Melanoma Cell Lines SK-MEL-5 and SK-MEL-28 in vitro

1319 views | Aug 24 2017

Lauren Green found that concentrations of RG2833 that effectively inhibited HDAC activity also resulted in reduced melanoma cell growth and viability. These results demonstrate the effectiveness of RG2833 in reducing the growth and viability of malignant melanoma cells in vitro and warrant further investigation of the potential therapeutic use of RG2833 and related compounds in the battle against cancer. [Read the Full Post]

Differential compensation mechanisms define resistance to PI3K inhibitors in PIK3CA amplified HNSCC

612 views | Aug 24 2017

Michmerhuizen NL et al. suggestED that inhibition of the PI3K and Ras-MEK-ERK pathways might be effective in some HNSCC patients; however, it also prompts the study of additional resistance mechanisms to identify synergistic combination therapies for tumors resistant to these di-therapies. [Read the Full Post]

Sodium phenylbutyrate antagonizes prostate cancer through the induction of apoptosis and attenuation of cell viability and migration

1417 views | Aug 23 2017

Xu Y et al. found that the viability of PCa cells was significantly inhibited by SPB treatment. As illustrated by flow cytometry, for DU145 cell line the average apoptotic rate of SPB-treated cells was significantly lower than that of the control group (P<0.05); similar results were also seen for PC3 (P<0.05). SPB administration also attenuated the colony formation and migration abilities in both cell lines. The expression level of survivin in SPB-treated cells was significantly downregulated, while the phosphorylation of p-38 and ERK was enhanced. Furthermore, in vivo tumor formation of both cell lines was suppressed by SPB as well. [Read the Full Post]

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway

1536 views | Aug 23 2017

Yun T et al. found that histone deacetylase (HDAC) inhibitors, including butyrate, augment Lys-120 acetylation of p53 and thus Apaf-1 expression by inhibiting HDAC1. In p53-null cells, transfection of wild-type but not K120R mutant p53 can restore the p53-dependent sensitivity to butyrate. Strikingly, transfection of acetylation-mimicking K120Q mutant p53 is sufficient to up-regulates Apaf-1 in a manner independent of butyrate treatment. Therefore, HDAC inhibitors can induce p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. [Read the Full Post]

Targeted knockdown of polo-like kinase 1 alters metabolic regulation in melanoma

763 views | Aug 22 2017

Gutteridge RE et al. suggested that PLK1 may be an important regulator of metabolism maintenance in melanoma cells. [Read the Full Post]

Vacuolin-1 inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition

751 views | Aug 22 2017

Sano O et al. concluded that PIKfyve inhibitors are novel chemical tools for regulating autophagy. [Read the Full Post]

Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways

759 views | Aug 21 2017

Zhang L et al. showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. [Read the Full Post]

Checkpoint kinase inhibitor AZD7762 strongly sensitises urothelial carcinoma cells to gemcitabine

1409 views | Aug 20 2017

Isono M et al. showed that AZD7762 enhanced sensitivity of urothelial carcinoma cells to gemcitabine by inhibiting DNA repair and disturbing checkpoints. Combining gemcitabine with CHK1 inhibition holds promise for urothelial cancer therapy. [Read the Full Post]

Plasmonic nanocarrier grid-enhanced Raman sensor for studies of anticancer drug delivery

960 views | Aug 20 2017

Kurzątkowska K et al. demonstrated that the proposed nanocarrier SERS sensor can be utilized to investigate attachment of targeting ligands to nanocarriers (attachment of folic acid ligand recognized by folate receptors of cancer cells is described). Further testing of the nanocarrier SERS sensor involved drug release induced by lowering pH and increasing GSH levels, both occurring in cancer cells. The proposed sensor can be utilized for a variety of drugs and targeting ligands, including those which are Raman inactive, since the linkers can act as the Raman markers, as illustrated with mercaptobenzoic acid and para-aminothiophenol. [Read the Full Post]

Hyperactivation of ATM upon DNA-PKcs inhibition modulates p53 dynamics and cell fate in response to DNA damage

0 views | Aug 19 2017

Finzel A et al. revealed a new regulatory interplay in which loss of DNA-PKcs function leads to hyperactivation of ATM and amplification of the p53 response, sensitizing cells for damage-induced senescence. [Read the Full Post]

Downregulation of GLUT4 contributes to effective intervention of estrogen receptor-negative/HER2-overexpressing early stage breast disease progression by lapatinib

0 views | Aug 19 2017

Acharya S et al. indicated that lapatinib, through its inhibition of key signaling pathways and tumor-promoting metabolic events, is a promising agent for the prevention/early intervention of ER-/HER2+ breast cancer progression. [Read the Full Post]

TIMP-1 expression induced by IL-32 is mediated through activation of AP-1 signal pathway

0 views | Aug 18 2017

Xu H, et al. believed that IL-32 might be involved in the pathogenesis of hepatic fibrosis by inducing TIMP-1 expression. [Read the Full Post]

Phosphorylation of the RNA-binding protein Dazl by MAPKAP kinase 2 regulates spermatogenesis

0 views | Aug 18 2017

Williams PA et al. suggested that signaling by the p38-MK2 pathway is a negative regulator of spermatogenesis via phosphorylation of Dazl. [Read the Full Post]

Interleukin 6 induces cell proliferation of clear cell renal cell carcinoma by suppressing hepaCAM via the STAT3-dependent up-regulation of DNMT1 or DNMT3b

1245 views | Aug 17 2017

Quan Z et al. provided a novel signal pathway regulating cell proliferation, potentially representing a therapeutic target for RCC. [Read the Full Post]

Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

1191 views | Aug 17 2017

Dai M et al. demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss. [Read the Full Post]

An FGFR inhibitor converts the tumor promoting effect of TGF-β by the induction of fibroblast-associated genes of hepatoma cells

2258 views | Aug 16 2017

Zhang HR et al. indicated that FGFR inhibitor treatment converts the effect of TGF-β on the hepatocellular carcinoma cells from tumor promotion into tumor inhibition by enhancing the induction effect of TGF-β on some fibroblast-associated genes. Converting human liver cancer cells into less malignant fibroblast-like cells and inducing tumor parenchyma cell fibrosis provides an alternative strategy for limiting tumor progression. [Read the Full Post]