Blog of Signaling Pathways

Identifying Regulatory Posttranslational Modifications of PD-L1: A Focus on Monoubiquitinaton

689 views | Aug 04 2018

Horita H et al. highlights the significance of identifying novel PTMs for PD-L1 and reveals potentially critical regulatory mechanisms that may be valuable therapeutic targets. In a broader context, this report validates an approach whereby one can gain insight into novel mechanisms of action by a simple and unbiased analysis of a PTM profile of potentially any endogenous protein of interest. [Read the Full Post]

JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors

1174 views | Aug 02 2018

Gao SP et al. revealed a mechanism whereby JAK2 inhibition overcomes acquired resistance to EGFR inhibitors and support the use of combination therapy with JAK and EGFR inhibitors for the treatment of EGFR-dependent NSCLC. [Read the Full Post]

AR-42 induces apoptosis in human hepatocellular carcinoma cells via HDAC5 inhibition

1600 views | Aug 02 2018

Zhang M et al. demonstrated for the first time that AR-42 targets HDAC5 and induces apoptosis in human hepatocellular carcinoma cells. AR-42 therefore shows potential as a new drug candidate for HCC therapy. [Read the Full Post]

HDAC6 promotes cell proliferation and confers resistance to temozolomide in glioblastoma

1283 views | Aug 01 2018

Wang Z et al. suggested that the inhibition of HDAC6 may be a promising strategy for the treatment of glioblastoma. [Read the Full Post]

Activation of the IGF1R pathway potentially mediates acquired resistance to mutant-selective 3rd-generation EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer

1372 views | Aug 01 2018

Park JH et al. suggested that activation of the IGF1R pathway associated with IGFBP3 loss can induce an acquired resistance to the mutant-selective EGFR-TKI, WZ4002. Therefore, a combined therapy of IGF1R inhibitors and mutant-selective EGFR-TKIs might be a viable treatment strategy for overcoming acquired resistance. [Read the Full Post]

HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions

4185 views | Jul 31 2018

Yu J et al. suggested that HDAC6 inhibition is a potent therapeutic strategy against inflammatory injury to endothelial cells. [Read the Full Post]

The histone deacetylase inhibitor valproic acid inhibits NKG2D expression in natural killer cells through suppression of STAT3 and HDAC3

1220 views | Jul 31 2018

Ni L et al. showed that VPA is a potent inhibitor of STAT3 phosphorylation and demonstrate that histone acetylation and STAT3 tyrosine705 phosphorylation cooperate in regulating NKG2D expression in NK cells. [Read the Full Post]

Long-term acquired everolimus resistance in pancreatic neuroendocrine tumours can be overcome with novel PI3K-AKT-mTOR inhibitors

662 views | Jul 30 2018

Vandamme T et al. indicated that long-term everolimus resistance was induced in two human PNET cell lines. Novel PI3K-AKT-mTOR pathway-targeting drugs can overcome everolimus resistance. Differential gene expression profiles suggest different mechanisms of everolimus resistance in BON-1 and QGP-1. [Read the Full Post]

Inhibition of JNK-mediated autophagy enhances NSCLC cell sensitivity to mTORC1/2 inhibitors

665 views | Jul 30 2018

Jin HO et al. suggested that combining mTORC1/2 inhibitors with inhibitors of JNK or autophagy might be an effective approach for improving therapeutic outcomes in NSCLC. [Read the Full Post]

Identification of mTOR as a primary resistance factor of the IAP antagonist AT406 in hepatocellular carcinoma cells

1245 views | Jul 29 2018

Zhen MC et al. showed that AT406 induced degradation of IAPs (cIAP-1 and XIAP), but didn't affect another anti-apoptosis protein Mcl-1. Co-treatment of OSI-027 caused simultaneous Mcl-1 downregulation to overcome AT406's resistance. Significantly, shRNA knockdown of Mcl-1 remarkably facilitated AT406-induced apoptosis in HCC cells. In vivo, AT406 oral administration suppressed HepG2 tumor growth in nude mice. Its activity was potentiated with co-administration of OSI-027. We conclude that mTOR could be a key resistance factor of AT406 in HCC cells. [Read the Full Post]

Cellular Prion Protein Mediates Pancreatic Cancer Cell Survival and Invasion through Association with and Enhanced Signaling of Notch1

1393 views | Jul 29 2018

Wang Y et al. unraveled a novel molecular pathway driven by interactions between PrP and Notch1 in the progression of PDAC, supporting a critical tumor-promoting role of Notch1 in PrP-expressing PDAC tumors. [Read the Full Post]

Acute hyperglycemia suppresses left ventricular diastolic function and inhibits autophagic flux in mice under prohypertrophic stimulation

816 views | Jul 28 2018

Xie J et al. found that acute hyperglycemia suppresses diastolic function, damages mitochondrial energy signaling, and inhibits autophagic flux in prohypertrophic factor-stimulated cardiomyocytes. [Read the Full Post]

GD2 ganglioside specific antibody treatment downregulates PI3K/Akt/mTOR signaling network in human neuroblastoma cell lines

810 views | Jul 28 2018

Durbas M et al. extended knowledge on mechanisms of action of the 14G2a mAb on the neuroblastoma cells. [Read the Full Post]

Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation

1452 views | Jul 27 2018

Figueiredo M et al. offered novel evidence on the role of Notch signalling in T/PT common primordium development, in an Hh-dependent manner. [Read the Full Post]

Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis

1398 views | Jul 27 2018

Hasebe T et al. provided evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development. Stem Cells 2017;35:1028-1039. [Read the Full Post]

The combination of irreversible EGFR TKIs and SAHA induces apoptosis and autophagy-mediated cell death to overcome acquired resistance in EGFR T790M-mutated lung cancer

745 views | Jul 26 2018

Lee TG et al. found that the combination of new generation EGFR TKIs and SAHA may be a new strategy to overcome the acquired resistance to EGFR TKIs in T790M mutant lung cancer. [Read the Full Post]

GSK621 Targets Glioma Cells via Activating AMP-Activated Protein Kinase Signalings

781 views | Jul 26 2018

Jiang H et al. summarized that GSK621 inhibits human glioma cells possibly via activating AMPK signaling. This novel AMPK activator could be a novel and promising anti-glioma cell agent. [Read the Full Post]

Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cells in vitro and in vivo by modulating multiple cellular pathways

949 views | Jul 25 2018

Yang T et al. indicated that CuB interferes with multiple cellular pathways in MM cells. CuB thus represents a promising therapeutic tool for the treatment of MM. [Read the Full Post]

Aberrant Notch Signaling in the Bone Marrow Microenvironment of Acute Lymphoid Leukemia Suppresses Osteoblast-Mediated Support of Hematopoietic Niche Function

1496 views | Jul 25 2018

Wang W et al. suggested that therapeutically targeting the leukemia-infiltrated hematopoietic niche may restore HSPC homeostasis and improve the outcome of ALL patients. [Read the Full Post]

Oxidative stress induces mitotic arrest by inhibiting Aurora A-involved mitotic spindle formation

882 views | Jul 24 2018

Wang GF et al. identified a mechanism by which ROS regulate mitotic progression and indicated a potential molecular target for the treatment of oxidative stress-related diseases. [Read the Full Post]