RNAi-mediated down-regulation of alpha-actinin-4 decreases invasion potential in oral squamous cell carcinoma.
alpha-actinin-4, originally identified as an actin-binding protein associated with cell motility, invasion, and metastasis of cancer cells, appears to be overexpressed in various human epithelial carcinomas, including colorectal, breast, esophageal, ovarian, and non-small cell lung carcinomas. The authors evaluated whether alpha-actinin-4 might be appropriate as a molecular target for cancer gene therapy. In 64 primary oral squamous cell carcinomas (OSCCs) and 10 normal oral mucosal specimens, and in seven human OSCC cell lines, alpha-actinin-4 expression was evaluated immunologically and correlations with clinicopathologic factors were examined. Overexpression of alpha-actinin-4 was detected in 38 of 64 oral squamous cell carcinomas (70%); significantly more frequently than in normal oral mucosa. The expression of alpha-actinin-4 was significantly associated with invasion potential defined by the Matrigel invasion assay. Cancer cell lines with higher alpha-actinin-4 expression had greater invasive potential. An RNAi-mediated decrease in alpha-actinin-4 expression reduced the invasion potential. These results indicated that the overexpression of alpha-actinin-4 was associated with an aggressive phenotype of OSCC. The study indicated that alpha-actinin-4 could be a potential molecular target for gene therapy by RNAi targeting for OSCC.
Yamada
S
S
Department of Oral and Maxillofacial Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. shinshin@nagasaki-u.ac.jp
Yanamoto
S
S
Yoshida
H
H
Yoshitomi
I
I
Kawasaki
G
G
Mizuno
A
A
Nemoto
T K
TK
D000185:Actinin / Q000032:analysis / Q000235:genetics*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000648:ultrastructure; D003593:Cytoplasm / Q000648:ultrastructure; D015194:Diffusion Chambers, Culture; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics; D009367:Neoplasm Staging; D010641:Phenotype; D034622:RNA Interference / Q000502:physiology*; D034741:RNA, Small Interfering / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction
C111453:ACTN4 protein, human; D034741:RNA, Small Interfering; D000185:Actinin