Short interfering RNA directed against TWIST, a novel zinc finger transcription factor, increases A549 cell sensitivity to cisplatin via MAPK/mitochondrial pathway

Previous reports have implicated epithelial–mesenchymal transition (EMT) as a major cause of cancer. TWIST, a novel zinc finger transcription factor, was suggested to be an important inducer of EMT and therefore be involved in different phases of tumorigenicity. However, whether TWIST suppression co...

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Published in:Biochemical and biophysical research communications 2008-05, Vol.369 (4), p.1098-1102
Main Authors: Zhuo, Wen-Lei, Wang, Yan, Zhuo, Xian-Lu, Zhang, Yun-Song, Chen, Zheng-Tang
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis
Cell Line, Tumor
Cell Survival - drug effects
Cisplatin
Cisplatin - pharmacology
Drug Resistance, Neoplasm - genetics
Epithelial–mesenchymal transition
Genetic Vectors
Humans
JNK Mitogen-Activated Protein Kinases - metabolism
Lung Neoplasms - enzymology
Lung Neoplasms - metabolism
MAP Kinase Signaling System
MAPKs
Mitochondria - enzymology
Mitochondrial pathway
Non-small cell lung cancer
Nuclear Proteins - antagonists & inhibitors
Nuclear Proteins - genetics
RNA Interference
RNA, Small Interfering - genetics
Sensitivity
TWIST
Twist-Related Protein 1 - antagonists & inhibitors
Twist-Related Protein 1 - genetics
Zinc Fingers
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Summary:Previous reports have implicated epithelial–mesenchymal transition (EMT) as a major cause of cancer. TWIST, a novel zinc finger transcription factor, was suggested to be an important inducer of EMT and therefore be involved in different phases of tumorigenicity. However, whether TWIST suppression could increase chemosensitivity of cancer cells to chemotherapeutic agent remains unclear. In the present study, we utilized RNA interference to knockdown TWIST expression in A549 cells and further assessed the cell viability and apoptosis as well as possible MAPKs and mitochondrial pathways. The data showed that TWIST depletion significantly sensitized A549 cells to cisplatin by inducing activation of JNK/mitochondrial pathway but not ERK and p-38 pathways, suggesting critical roles of TWIST in A549 cell chemoresistance to cisplatin and raising the possibility of TWIST depletion as a promising approach to lung cancer therapy.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.02.143