title: Forkhead box C1 induces epithelial‑mesenchymal transition and is a potential therapeutic target in nasopharyngeal carcinoma.
abstract: Nasopharyngeal carcinoma (NPC) is a highly invasive malignancy with cervical lymphopathy as the initial presentation. Epithelial‑mesenchymal transition (EMT), a process by which epithelial cells lose cell‑cell adhesion and gain migratory and invasive properties, has a pivotal role in metastasis. Forkhead box C1 (FoxC1), a member of the forkhead family of transcription factors, induces EMT and has a critical role in metastasis of multiple human cancers. However, the role of FoxC1 in the progression of NPC has remained elusive. The present study revealed that the expression of FoxC1 was markedly elevated in NPC tissues compared with that in chronically inflamed nasopharyngeal tissues and was closely correlated with vimentin, fibronectin and N‑cadherin expression as indicated by immunohistochemical assays. In addition, high FoxC1 expression was positively associated with lymph node metastasis, distant metastasis and an advanced clinical stage in patients with NPC. Furthermore, FoxC1 expression was high in NPC cell lines while being low in an immortalized normal nasopharyngeal epithelial cell line. In vitro, knockdown of FoxC1 in the CNE2 human NPC cell line by small interfering RNA downregulated vimentin, fibronectin and N‑cadherin expression and reduced the migratory and invasive capacity of CNE2 cells. In conclusion, the present study indicated that FoxC1 has a pivotal role in EMT through the upregulation of vimentin, fibronectin and N‑cadherin expression. Thus, FoxC1 may be a potential therapeutic target in NPC.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ou-Yang
authors.affiliation: Department of Pathology, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541199, P.R. China.
authors.forename: Sheng-Jun
authors.initials: SJ
authors.lastname: Xiao
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P.R. China.
authors.forename: Shi-Jang
authors.initials: SJ
authors.lastname: Yi
authors.affiliation: Department of Physiology, Faculty of Basic Medical Science, Guilin Medical University, Guilin, Guangxi 541004, P.R. China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: The liver Disease Center of The PLA, The 458th Hospital of The PLA, Guangzhou, Guangdong 510602, P.R. China.
authors.forename: Shi
authors.initials: S
authors.lastname: Ou-Yang
authors.affiliation: Department of Public Health College, Guilin Medical University, Guilin, Guangxi 541004, P.R. China.
authors.forename: Sheng-Kui
authors.initials: SK
authors.lastname: Tan
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P.R. China.
authors.forename: Xun
authors.initials: X
authors.lastname: Lei
mesh_terms: D000328:Adult; D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D015820:Cadherins; C112743:FOXC1 protein, human; D005353:Fibronectins; D051858:Forkhead Transcription Factors; D034741:RNA, Small Interfering; D014746:Vimentin