Knockdown of S100A4 impairs arecoline-induced invasiveness of oral squamous cell carcinomas.
OBJECTIVE
Metastasis is the most common cause of oral squamous cell carcinoma (OSCC)-related death. The physiological function of S100A4 in the pathogenesis of areca quid chewing-associated OSCC has not been uncovered.


METHODS
OSCC tissues from areca quid chewers were analyzed by immunohistochemistry for S100A4 expression. The functions of S100A4 in invasiveness of arecoline-treated oral epithelial (OE) cells were determined by loss function approaches.


RESULTS
Expression of S100A4 was positively correlated with clinical grading and lymph node metastasis of OSCC. Upregulated S100A4 is correlated with poor survival outcome of OSCC patients. Arecoline led to dose-dependent elevation of S100A4 expression in oral epithelial (OE) cells. Down-regulation of S100A4 significantly reversed arecoline-induced oncogenecity in OE cells. The additions of pharmacological agents LY294002, SP600125, and CAY10585 were found to inhibit arecoline-induced S100A4 expression in OE cells.


CONCLUSIONS
Arecoline-induced S100A4 expression was down-regulated by LY294002, SP600125, or CAY10585 treatment. Targeting S100A4 might offer a new strategy for the treatment of OSCC patients with metastasis.
School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
Fang-Wei
FW
Hu
School of Public Health, Chung Shan Medical University, Taichung, Taiwan.
Shiuan-Shinn
SS
Lee
School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
Li-Chiu
LC
Yang
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan.
Chung-Hung
CH
Tsai
Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
Tong-Hong
TH
Wang
School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan. Electronic address: myc@csmu.edu.tw.
Ming-Yung
MY
Chou
School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan. Electronic address: ccyu@csmu.edu.tw.
Cheng-Chia
CC
Yu
D000873:Anthracenes / Q000494:pharmacology; D001114:Areca / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000401:mortality / Q000473:pathology*; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008409:Mastication; D009025:Morpholines / Q000494:pharmacology; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000401:mortality / Q000473:pathology*; D009361:Neoplasm Invasiveness; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000187:drug effects / Q000378:metabolism*; D015996:Survival Rate
D000873:Anthracenes; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; C432165:pyrazolanthrone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Arecoline; Invasiveness; Oncogenecity; Oral squamous cell carcinomas; S100A4