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Epithelial to mesenchymal transition might be induced via CD44 isoform switching in colorectal cancer
Author(s) -
Mashita Naoki,
Yamada Suguru,
Nakayama Goro,
Tanaka Chie,
Iwata Naoki,
Kanda Mitsuro,
Kobayashi Daisuke,
Fujii Tsutomu,
Sugimoto Hiroyuki,
Koike Masahiko,
Nomoto Shuji,
Fujiwara Michitaka,
Kodera Yasuhiro
Publication year - 2014
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.23705
Subject(s) - cd44 , vimentin , colorectal cancer , epithelial–mesenchymal transition , medicine , cancer research , cancer , gene knockdown , mesenchymal stem cell , immunohistochemistry , oncology , pathology , cell , metastasis , biology , cell culture , genetics
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. J. Surg. Oncol. 2014 110:745–751 . © 2014 Wiley Periodicals, Inc.