title: NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma.
abstract: Head and neck cancer, including oral squamous cell carcinoma, is the sixth most common cancer worldwide. Although cancer cell invasion and metastasis are crucial for tumor progression, detailed molecular mechanisms underlying the invasion and metastasis of oral squamous cell carcinoma are unclear. Comparison of transcriptional profiles using a cDNA microarray demonstrated that N4BP2L1, a novel oncogene expressed by neural precursor cells, is involved in oral squamous cell carcinoma. Expression of N4BP2L1 in oral squamous cell carcinoma is regulated by activation of miR-448 and is higher than in normal oral mucosa. Knockdown of N4BP2L1 and upregulation of miR-448 significantly reduced the invasive potential of oral squamous cell carcinoma cells. We studied N4BP2L1 expression in 187 cases of oral squamous cell carcinoma and found its overexpression to be significantly associated with nodal metastasis (P = 0.0155) and poor prognosis (P = 0.0136). Expression of miR-448 was found to be inversely associated with that of N4BP2L1 (P = 0.0019). Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (P = 0.0349). Our results suggest that N4BP2L1 plays an important role in tumor cell invasion in oral squamous cell carcinoma. Further studies on expression of N4BP2L1 may provide new insight into its function and clarify its potential as biomarker in human oral cancer.
authors.affiliation: Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan. sasa@naramed-u.ac.jp.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sasahira
authors.affiliation: Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.|Department of Oral and Maxillofacial Surgery, Nara Medical University, Kashihara, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Kurihara
authors.affiliation: Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nishiguchi
authors.affiliation: Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.
authors.forename: Rina
authors.initials: R
authors.lastname: Fujiwara
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nara Medical University, Kashihara, Japan.
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Kirita
authors.affiliation: Department of Molecular Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D058953:Neural Stem Cells / Q000166:cytology*
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C000614200:NEDD 4 binding protein 2-like 1 protein, human
keywords: Invasion; Metastasis; N4BP2L1; Oral cancer; miR-448