title: Aberrant expression of connexin 26 is associated with lung metastasis of colorectal cancer.
abstract: OBJECTIVE
  Connexin 26 (Cx26) is one of the gap junction-forming family members classically considered to be tumor suppressors. However, recent studies show association of elevated expression of Cx26 with poor prognosis in several human malignancies. Furthermore, Cx26 has been observed to be indispensable to spontaneous metastasis of melanoma cells. Here, we assessed Cx26 expression in primary colorectal cancer (CRC) and the metastatic lesions to elucidate its role in metastasis.
  
  
  METHODS
  Cx26 expression was assessed in 25 adenomas, 167 CRCs, and normal mucosa, together with the metastatic lesions.
  
  
  RESULTS
  Normal mucosa and adenomatous tissue expressed Cx26 mainly in the plasma membrane, whereas cancer cells mostly contained Cx26 in the cytoplasm. The incidence of aberrant Cx26 expression varied widely in CRC (mean, 49.5 +/- 35.5%), and the expression levels were confirmed by Western blot and quantitative reverse transcription-PCR. Clinicopathologic survey revealed association of high expression with less differentiated histology and venous invasion (P = 0.0053 and P = 0.0084, respectively). Notably, high Cx26 expression was associated with shorter disease-free survival and shorter lung metastasis-free survival in 154 curatively resected CRC sets (P = 0.041 and P = 0.028, respectively). Survey of metastatic lesions revealed that lung metastasis, but not liver and lymph nodes metastases, expressed higher Cx26 than the CRC series or corresponding primary CRCs (P < 0.0001 and P = 0.0001, respectively).
  
  
  CONCLUSIONS
  These findings suggest that aberrant expression of Cx26 plays an essential role in lung metastasis. Thus, Cx26 is a promising therapeutic target, particularly for CRC patients who develop lung metastasis.
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamada-oka, Suita City, Osaka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ezumi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kohei
authors.initials: K
authors.lastname: Murata
authors.forename: Masahiko
authors.initials: M
authors.lastname: Higashiyama
authors.forename: Bazarragchaa
authors.initials: B
authors.lastname: Damdinsuren
authors.forename: Yurika
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Naganori
authors.initials: N
authors.lastname: Kyo
authors.forename: Jiro
authors.initials: J
authors.lastname: Okami
authors.forename: Chew Yee
authors.initials: CY
authors.lastname: Ngan
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.forename: Masataka
authors.initials: M
authors.lastname: Ikeda
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Sekimoto
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nojima
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction
chemical_list: D017630:Connexins; D017931:DNA Primers; C000607042:GJB2 protein, human; D000072259:Connexin 26