title: Epithelial to mesenchymal transition might be induced via CD44 isoform switching in colorectal cancer.
abstract: BACKGROUND
  Isoform switching of CD44 is associated with epithelial to mesenchymal transition (EMT) in several cancers; however, the clinical implications of this remain unclear for colorectal cancer (CRC).
  
  
  METHODS
  We measured expression levels of E-cadherin, vimentin, CD44 standard (CD44s) and CD44 variant 9 (CD44v9) transcripts in 14 CRC cell lines and 150 CRC patients. We determined EMT and CD44 status by calculating vimentin/E-cadherin and CD44s/CD44v9 expression ratios, respectively. Associations between EMT status and CD44 isoform switching, and between clinicopathological factors and prognosis were analyzed.
  
  
  RESULTS
  CD44s was highly expressed in mesenchymal-type cell lines, while CD44v9 was highly expressed in epithelial-type cell lines. CD44 knockdown resulted in decreased levels of vimentin expression, and significantly reduced proliferation, migration and invasion of cells. In CRC patients, the mesenchymal group and the high CD44 status group exhibited significantly poorer survival than that for the epithelial group (5-year survival; 62.1% vs. 85.5%, P = 0.0085) and the low CD44 status group (5-year survival; 66.1% vs. 85.0%, P = 0.0251). On multivariate analysis, CD44 status was an independent prognostic factor.
  
  
  CONCLUSIONS
  The status of EMT and CD44 is a critical prognostic factor, with CD44 isoform switching a possible trigger for EMT in CRC.
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Naoki
authors: N
authors: Mashita
authors: Suguru
authors: S
authors: Yamada
authors: Goro
authors: G
authors: Nakayama
authors: Chie
authors: C
authors: Tanaka
authors: Naoki
authors: N
authors: Iwata
authors: Mitsuro
authors: M
authors: Kanda
authors: Daisuke
authors: D
authors: Kobayashi
authors: Tsutomu
authors: T
authors: Fujii
authors: Hiroyuki
authors: H
authors: Sugimoto
authors: Masahiko
authors: M
authors: Koike
authors: Shuji
authors: S
authors: Nomoto
authors: Michitaka
authors: M
authors: Fujiwara
authors: Yasuhiro
authors: Y
authors: Kodera
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014746:Vimentin / Q000378:metabolism; D055815:Young Adult
chemical_list: C497483:CD44 protein, human; D015820:Cadherins; D018960:Hyaluronan Receptors; D020033:Protein Isoforms; D014746:Vimentin
keywords: CD44; colorectal cancer; epithelial to mesenchymal transition