title: Forkhead box protein C2 contributes to invasion and metastasis of extrahepatic cholangiocarcinoma, resulting in a poor prognosis.
abstract: Extrahepatic cholangiocarcinoma (EHCC) is a cancer with a poor prognosis, and the postoperative survival of patients depends on the existence of invasion and metastasis. The epithelial-to-mesenchymal transition (EMT) is an important step in EHCC invasion and metastasis. Forkhead box protein C2 (FOXC2) is a transcription factor that has been reported to induce the EMT. Therefore we examined the correlation between FOXC2 expression and clinical pathological factors, and analysed the function of FOXC2. The expression of FOXC2 in 77 EHCC cases was investigated by immunohistochemical staining, and the relationship between FOXC2 expression and clinicopathological factor was assessed. Knockdown by small interfering RNA (siRNA) was performed to determine the roles of FOXC2 in EHCC cell line. FOXC2 expression correlated with lymph node metastasis (P = 0.0205). Patients in the high FOXC2 expression group had a poorer prognosis than the patients in the low FOXC2 expression group. Moreover, FOXC2 knockdown inhibited cell motility and invasion, and decreased the expression of EMT markers (N-cadherin, and matrix metalloproteinase (MMP) -2) and Angiopietin-2 (Ang-2). The EMT inducer FOXC2 contributes to a poor prognosis and cancer progression. FOXC2 may be a promising molecular target for regulating EHCC metastasis.
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.forename: Hideki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokobori
authors.forename: Bolag
authors.initials: B
authors.lastname: Altan
authors.forename: Norio
authors.initials: N
authors.lastname: Kubo
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Araki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Wada
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Mochida
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sasaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Kashiwabara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hosouchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001650:Bile Duct Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D018281:Cholangiocarcinoma / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D018572:Disease-Free Survival; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D051858:Forkhead Transcription Factors; C555023:VPS51 protein, human; D033921:Vesicular Transport Proteins; C082078:mesenchyme fork head 1 protein; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
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