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.
Department of Respiratory Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, PR China.
Li
L
Li
Department of Respiratory Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, PR China. Electronic address: meitonghuacmu@126.com.
Dr Tonghua
DT
Mei
Department of Orthopedics Surgery, Dujiangyan People's Hospital, Dujiangyan, 611830 Sichuan, PR China.
Yun
Y
Zeng
D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
D005353:Fibronectins; C498143:RELA protein, human; D051996:Transcription Factor RelA; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2
Fibronectin; HDAC2; Migration; NSCLC; p65