scholarly journals PD‐L1 positively regulates MET phosphorylation through inhibiting PTP1B

2021 ◽  
Author(s):  
Shangyun Lu ◽  
Zhenou Sun ◽  
Wenli Hu ◽  
Shutao Yin ◽  
Chong Zhao ◽  
...  
Keyword(s):  
Met Phosphorylation

scholarly journals Anti-neoplastic Effect of Ginkgolide C through Modulating c-Met Phosphorylation in Hepatocellular Carcinoma Cells

2020 ◽  
Vol 21 (21) ◽  
pp. 8303
Author(s):  
Min Hee Yang ◽  
Seung Ho Baek ◽  
Jae-Young Um ◽  
Kwang Seok Ahn
Keyword(s):  
Hepatocellular Carcinoma ◽  
Invasion And Migration ◽  
Oncogenic Pathways ◽  
Tumor Growth And Metastasis ◽  
And Migration ◽  
Induced Apoptosis ◽  
Interfering Rna ◽  
Hepatocyte Growth ◽  
Hcc Cells ◽  
Met Phosphorylation

Ginkgolide C (GGC) derived from Ginkgo biloba, has been reported to exhibit various biological functions. However, the anti-neoplastic effect of GGC and its mechanisms in liver cancer have not been studied previously. Hepatocyte growth factor (HGF)/c-mesenchymal–epithelial transition receptor (c-Met) pathway can regulate tumor growth and metastasis in hepatocellular carcinoma (HCC) cells. This study aimed to evaluate the anti-neoplastic effect of GGC against HCC cells and we observed that GGC inhibited HGF-induced c-Met and c-Met downstream oncogenic pathways, such as PI3K/Akt/mTOR and MEK/ERK. In addition, GGC also suppressed the proliferation of expression of diverse tumorigenic proteins (Bcl-2, Bcl-xL, Survivin, IAP-1, IAP-2, Cyclin D1, and COX-2) and induced apoptosis. Interestingly, the silencing of c-Met by small interfering RNA (siRNA) mitigated c-Met expression and enhanced GGC-induced apoptosis. Moreover, it was noted that GGC also significantly reduced the invasion and migration of HCC cells. Overall, the data clearly demonstrate that GGC exerts its anti-neoplastic activity through modulating c-Met phosphorylation and may be used as an effective therapy against HCC.

The role of c-Met inhibition for neuroblastoma treatment.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10041-10041
Author(s):  
Peter Zage ◽  
Kathy Scorsone ◽  
Linna Zhang
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Neuroblastoma Tumor ◽  
Met Phosphorylation

10041 Background: Neuroblastoma is the most common extra-cranial solid tumor of childhood. Many children present with high-risk disease characterized by rapid tumor growth, resistance to chemotherapy, and widespread metastasis, and novel therapies are needed. Previous studies have identified a role for the HGF/c-Met pathway in the pathogenesis of neuroblastoma. We hypothesized that EMD1214063 would be effective against neuroblastoma tumor cells and tumors in preclinical models via inhibition of HGF/c-Met signaling. Methods: We determined the expression of c-Met in a panel of neuroblastoma tumor cells and neuroblastoma cell viability after treatment with EMD1214063 using MTT assays. Analyses were performed for changes in cell morphology, cell cycle progression, and cell death via apoptosis after EMD1214063 treatment. To investigate the efficacy of EMD1214063 against neuroblastoma tumors in vivo, neuroblastoma cells were injected orthotopically into immunocompromised mice, and the mice in which tumors developed were treated with oral EMD1214063. Results: All neuroblastoma cell lines were sensitive to EMD1214063, and IC50 values ranged from 2.4 - 8.5 mcM. EMD1214063 treatment inhibited HGF-mediated c-Met phosphorylation in neuroblastoma cells. EMD1214063 induced cell cycle arrest in neuroblastoma tumor cells with high c-Met expression, and induced apoptosis in all tested cell lines. In mice with neuroblastoma xenograft tumors, EMD1214063 inhibited tumor growth. Conclusions: Treatment of neuroblastoma tumor cells with EMD1214063 inhibits HGF-induced c-Met phosphorylation and results in cell death. Furthermore, EMD1214063 induces cell cycle arrrest prior to cell death in neuroblastoma tumor cells with high c-Met expression. EMD1214063 treatment is effective in reducing tumor growth in vivo in mice. Inhibition of c-Met represents a potential new therapeutic strategy for neuroblastoma, and further preclinical studies of EMD1214063 are warranted.

Association of c-Met phosphorylation with micropapillary pattern and small cluster invasion in pT1-size lung adenocarcinoma

Lung Cancer ◽  
2013 ◽  
Vol 82 (3) ◽  
pp. 413-419 ◽  
Author(s):  
Kaori Koga ◽  
Makoto Hamasaki ◽  
Fumiaki Kato ◽  
Mikiko Aoki ◽  
Hiroyuki Hayashi ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Small Cluster ◽  
Micropapillary Pattern ◽  
Met Phosphorylation

Expression of human kallikrein 1-related peptidase 4 (KLK4) and MET phosphorylation in prostate cancer tissue: immunohistochemical analysis

Human Cell ◽  
2015 ◽  
Vol 28 (3) ◽  
pp. 133-142 ◽  
Author(s):  
Shoichiro Mukai ◽  
Kenji Yorita ◽  
Koji Yamasaki ◽  
Takahiro Nagai ◽  
Toyoharu Kamibeppu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immunohistochemical Analysis ◽  
Cancer Tissue ◽  
Prostate Cancer Tissue ◽  
Met Phosphorylation

scholarly journals Development of a Cell-Based Assay for Measurement of c-Met Phosphorylation Using AlphaScreenTM Technology and High-Content Imaging Analysis

2009 ◽  
Vol 14 (4) ◽  
pp. 404-411 ◽  
Author(s):  
Nadya Smotrov ◽  
Anjili Mathur ◽  
Ilona Kariv ◽  
Christopher M. Moxham ◽  
Nathan Bays
Keyword(s):  
Kinase Activity ◽  
Kinase Inhibitors ◽  
Modular Design ◽  
Therapy Monitoring ◽  
Critical Role ◽  
High Content Imaging ◽  
Cellular Processes ◽  
Cell Proliferation And Differentiation ◽  
Transformed Cell Lines ◽  
Met Phosphorylation

c-Met is a receptor tyrosine kinase (RTK) with a critical role in many fundamental cellular processes, including cell proliferation and differentiation. Deregulated c-Met signaling has been implicated in both the initiation and progression of human cancers and therefore represents an attractive target for anticancer therapy. Monitoring the phosphorylation status of relevant tyrosine residues provides an important method of assessing c-Met kinase activity. This report describes a novel assay to monitor c-Met phosphorylation in cells using Amplified Luminescent Proximity Homogeneous Assay (AlphaScreen™) technology. Using AlphaScreen™, the authors were able to detect both global and site-specific phosphorylation of c-Met in transformed cell lines. Data obtained from the AlphaScreen™ assay were compared to data obtained from a high-content imaging (HCI) method developed in parallel to monitor c-Met phosphorylation at the single cell level. The AlphaScreen™ assay was miniaturized to a 384-well format with acceptable signal-to-background ratio (S/B) and Z′ statistics and was employed to measure c-Met kinase activity in situ after treatment with potent c-Met-specific kinase inhibitors. The authors discuss the utility of quantifying endogenous cellular c-Met phosphorylation in lead optimization and how the modular design of the AlphaScreen™ assay allows its adaptation to measure cellular activity of other kinases. ( Journal of Biomolecular Screening 2009:404-411)

Abstract 1019: The MET inhibitor tepotinib shows sustained effects on MET phosphorylation and viability in cellular washout experiments

2021 ◽  
Author(s):  
Nina Berges ◽  
Jan Henrik Klug ◽  
Anna Eicher ◽  
Jennifer Loehr ◽  
Daniel Schwarz ◽  
...  
Keyword(s):  
Sustained Effects ◽  
Met Inhibitor ◽  
Met Phosphorylation
Sign in / Sign up

Export Citation Format

Share Document