HDAC2 promotes the migration and invasion of non-small cell lung cancer cells via upregulation of fibronectin.
Recent studies indicated that histone deacetylases (HDACs) can modulate the tumorigenesis and development of cancer cells. We evaluated the expression of class I HDACs in non-small cell lung cancer (NSCLC) cells and found that HDAC2 was significantly increased in NSCLC cells as compared with the normal bronchial epithelial cell line BEAS-2B. Silencing of HDAC2 by its specific siRNAs can significantly inhibit the in vitro migration and invasion of A549 and H1395 cells. While over expression of HDAC2 by transfection of pcDNA/HDAC2 plasmid can trigger the motility of NSCLC cells. Over expression of HDAC2 increased the protein and mRNA expression of firbronectin (FN), which can accelerate the metastasis of cancer cells. Similarly, knock down of HDAC2 suppressed the expression of FN. The inhibitor of NF-κB, while not ERK1/2 or PI3K/Akt, attenuated HDAC2 induced up regulation of FN and invasion of NSCLC cells. Furthermore, HDAC2 can markedly increase both mRNA and protein levels of p65 in NSCLC cells. Collectively, our data revealed that HDAC2 can trigger migration and invasion of NSCLC cells via up regulation FN through activation of NF-κB. It suggested HDAC2 might be a potential therapeutic target for the drug development of NSCLC patients.
['Li|Li|L|', 'Mei|Dr Tonghua|DT|', 'Zeng|Yun|Y|']
D002289:Carcinoma, Non-Small-Cell Lung D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D005353:Fibronectins D015971:Gene Expression Regulation, Enzymologic D015972:Gene Expression Regulation, Neoplastic D056464:Histone Deacetylase 2 D006801:Humans D008175:Lung Neoplasms D009361:Neoplasm Invasiveness D034622:RNA Interference D015398:Signal Transduction D013997:Time Factors D051996:Transcription Factor RelA D014162:Transfection D015854:Up-Regulation
HDAC2 Migration Fibronectin NSCLC p65