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Repression of YAP by NCTD disrupts NSCLC progression
#MMPMID27903989
Guo J
; Wu Y
; Yang L
; Du J
; Gong K
; Chen W
; Dai J
; Li X
; Xi S
Oncotarget
2017[Jan]; 8
(2
): 2307-2319
PMID27903989
show ga
The efficacy of available lung cancer therapeutic interference is significantly
limited by various resistance mechanisms to those drugs. Activation of the
oncogene YAP underlying the initiation, progression, and metastasis of lung
cancer associates with poor prognosis and confers drug resistance against
targeted therapy. In this study, we evaluated the specificity of norcantharidin
(NCTD) in repressing YAP to inhibit non-small cell lung carcinoma (NSCLC)
progression. Our study revealed that YAP signal pathways were aberrantly
activated in lung cancer tissues and cells which rendered more proliferative and
invasive phenotypes to human lung cancer cells. We confirmed that NCTD
specifically repressed YAP signaling pathway to interfere the YAP-mediated
non-small cell lung carcinoma progression and metastasis via arresting cell
cycle, enhancing apoptosis and inducing senescence. We also found NCTD-mediated
repression of YAP decreased epithelial-to-mesenchymal transition (EMT) and
reduced the motile and invasive cellular phenotype in vitro via enhancing
E-cadherin and decreasing fibronectin/vimentin. Mechanistic investigations
revealed that NCTD transcriptionally downregulated YAP and post-translationally
modulated the subcellular redistribution of YAP between nucleus and cytoplasm.
Collectively, our results indicated that NCTD is a novel therapeutic drug
candidate for NSCLC which specifically and sensitively target YAP signal pathway.
|A549 Cells
[MESH]
|Adaptor Proteins, Signal Transducing/*antagonists &
inhibitors/genetics/metabolism
[MESH]
free
free
free
