title: Overexpression of c-fos promotes cell invasion and migration via CD44 pathway in oral squamous cell carcinoma.
abstract: BACKGROUND
  Oral squamous cell carcinoma (OSCC) is one of the most deadly malignant tumors with high invasive potential and frequently cervical lymph node metastasis. AP-1 plays a critical role in tumor invasion and metastasis, but there are few reports on the role of c-Fos in OSCC carcinogenesis and metastasis.
  
  
  METHODS
  Investigate c-Fos expression in clinical samples from 58 primary patients with OSCC by immunohistochemistry. c-Fos knockdown stable cell lines were established by lentiviral infection and transwell cell invasion assay to detect the effects of c-Fos knockdown on tumor cell invasion.
  
  
  RESULTS
  Nuclear and cytoplasmic c-Fos protein were both overexpression in cancerous tissues compared with adjacent non-malignant epithelia (nuclear: P < 0.001, cytoplasmic: P = 0.005). Higher level nuclear c-Fos expression was found in the tumor samples of patients with lymph node metastasis than those without lymph node metastasis (4.85 ± 1.43 vs. 3.61 ± 1.28, P = 0.002). Higher level of c-Fos expression was also found in tumor invasive front margin than tumor center and high nuclear expression of c-Fos indicated poor survival. Knockdown of c-Fos greatly suppressed tumor cell proliferation and invasion and downregulated CD44 and CyclinD1 expression in HN6 and SCC9 cells. However, CyclinD3, c-myc, and Erk1/2 were found no changes to c-Fos depletion.
  
  
  CONCLUSIONS
  c-Fos promoted cell invasion and migration via CD44 pathway in OSCC. c-Fos could be used as a potential therapeutic target gene and an additional marker for evaluation of lymph node metastasis.
authors.affiliation: Department of Oral and Cranio-Maxillofacial Science, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China; Shanghai Stomatological Disease Center, Shanghai, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Dong
authors.forename: Dong-Xia
authors.initials: DX
authors.lastname: Ye
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Zhang
authors.forename: Hong-Ya
authors.initials: HY
authors.lastname: Pan
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D055815:Young Adult
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D016760:Proto-Oncogene Proteins c-fos
keywords: immunohistochemistry; m c-Fos; oral squamous cell carcinoma; small RNA interference; tumor invasion and metastasis