Blog of Signaling Pathways

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

1592 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

796 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

773 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

781 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

1451 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

993 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

1277 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

1264 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

2391 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]

Lipopolysaccharide increases IL-6 secretion via activation of the ERK1/2 signaling pathway to up-regulate RANKL gene expression in MLO-Y4 cells

1248 views | Aug 16 2017

Yu K et al. indicated that LPS up-regulates osteocyte expression of RANKL and IL-6, and the increased RANKL is associated with the up-regulation of IL-6, which involves the ERK1/2 pathway. [Read the Full Post]

Cell Death Induction by the Indirubin Derivative 7BIO and the BH3 Mimetic Drugs ABT-737 and GX15-070 in Medullary Thyroid Carcinoma Cells

1974 views | Aug 15 2017

Broecker-Preuss M et al. showed that although the exact kind of cell death and target molecules of 7BIO and GX15-070 are not yet defined, direct induction of cell death may be a new therapeutic option in medullary thyroid carcinoma cells. [Read the Full Post]

Akt Activation Mediates Acquired Resistance to Fibroblast Growth Factor Receptor Inhibitor BGJ398

1153 views | Aug 15 2017

Datta J et al. suggested a role for Akt pathway in mediating acquired resistance to FGFR inhibition. [Read the Full Post]

Nuclear PTEN interferes with binding of Ku70 at double-strand breaks through post-translational poly(ADP-ribosyl)ation

724 views | Aug 14 2017

Guan J, et al. provided contributes to understanding the effect of PTEN in repair of DSB and using defined anti-tumor DSB drugs to treat tumor cells with aberrant PTEN. [Read the Full Post]

A novel sgRNA selection system for CRISPR-Cas9 in mammalian cells

2067 views | Aug 14 2017

Zhang H et al. provided a potential application to optimize the sgRNAs in different species and to generate a powerful CRISPR-Cas9 genome-wide screening system with minimum amounts of sgRNAs. [Read the Full Post]

Translationally controlled tumour protein TCTP is induced early in human colorectal tumours and contributes to the resistance of HCT116 colon cancer cells to 5-FU and oxaliplatin

769 views | Aug 13 2017

Wu J et al. indicated that TCTP might be suitable as a biomarker and that combinatorial treatment using 5-FU/oxaliplatin, together with mTOR kinase inhibitors, could be a route to preventing the development of resistance to these drugs. [Read the Full Post]

Preclinical evaluation of potential therapeutic targets in dedifferentiated liposarcoma

995 views | Aug 13 2017

Hanes R et al. indicated that FGFR inhibitors have therapeutic potential in the treatment of DDLPS with amplified FRS2. [Read the Full Post]