Dasatinib sensitises KRAS -mutant cancer cells to mitogen-activated protein kinase kinase inhibitor via inhibition of TAZ activity

2018 ◽  
Vol 99 ◽  
pp. 37-48 ◽  
Author(s):  
Guanhua Rao ◽  
In-kyu Kim ◽  
Fabio Conforti ◽  
Jing Liu ◽  
Yu-Wen Zhang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cancer Cells ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

scholarly journals Activity of the oral mitogen-activated protein kinase kinase inhibitor trametinib inRAS-mutant relapsed or refractory myeloid malignancies

Cancer ◽  
2016 ◽  
Vol 122 (12) ◽  
pp. 1871-1879 ◽  
Author(s):  
Gautam Borthakur ◽  
Leslie Popplewell ◽  
Michael Boyiadzis ◽  
James Foran ◽  
Uwe Platzbecker ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Myeloid Malignancies ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

scholarly journals Black Rice Anthocyanins Suppress Metastasis of Breast Cancer Cells by Targeting RAS/RAF/MAPK Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Xiang-Yan Chen ◽  
Jie Zhou ◽  
Li-Ping Luo ◽  
Bin Han ◽  
Fei Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Kinase ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Black Rice ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

Overexpression of human epidermal growth factor receptor 2 (HER2) drives the biology of 30% of breast cancer cases. As a transducer of HER2 signaling, RAS/RAF/MAPK pathway plays a pivotal role in the development of breast cancer. In this study, we examined the molecular mechanisms underlying the chemopreventive effects of black rice anthocyanins (BRACs) extract and identified their molecular targets in HER2+breast cancer cells. Treatment of MDA-MB-453 cells (HER2+) with BRACs inhibited cell migration and invasion, suppressed the activation of mitogen-activated protein kinase kinase kinase (RAF), mitogen-activated protein kinase kinase (MEK), and c-Jun N-terminal kinase (JNK), and downregulated the secretion of matrix metalloproteinase 2 (MMP2) and MMP9. BRACs also weakened the interactions of HER2 with RAF, MEK, and JNK proteins, respectively, and decreased the mRNA expression ofraf,mek, andjnk. Further, we found combined treatment with BRACs and RAF, MEK, or JNK inhibitors could enhance the antimetastatic activity, compared with that of each treatment. Transient transfection with small interfering RNAs (siRNAs) specific forraf,mek, andjnkinhibited their mRNA expression in MDA-MB-453 cells. Moreover, cotreatment with BRACs and siRNA induces a more remarkable inhibitory effect than that by either substance alone. In summary, our study suggested that BRACs suppress metastasis in breast cancer cells by targeting the RAS/RAF/MAPK pathway.

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