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Topic: Reviews of Recent Advances in Research and Treatment for
Gastroenterological Malignancies

Epithelial-mesenchymal transition in gastroenterological cancer

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Hirohisa Okabe , Kosuke Mima , Seiya Saito , Hiromitsu Hayashi , Katsunori Imai , Hidetoshi Nitta ,
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Daisuke Hashimoto , Akira Chikamoto , Takatoshi Ishiko , Toru Beppu , Hideo Baba 1
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1 Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
2 Department of Multidisciplinary Treatment for Gastroenterological Cancer, Kumamoto University Hospital, Kumamoto 860-8556, Japan.
Correspondence to: Prof. Hideo Baba, Department of Gastroenterological Surgery, Graduate School of Life Science, Kumamoto University, 1-1-1 Honjo,
Kumamoto City, Kumamoto 860-8556, Japan. Email: hdobaba@kumamoto-u.ac.jp
ABSTRACT
Epithelial-mesenchymal transition (EMT) was fi rst reported as an essential process in embryonic cells and later showed that
cancer cells, regardless of the context, exhibited a similar phenomenon that was crucial for tumor progression. Epithelial cells
lose their adhesive characteristic capacity which is necessary for their functions but gain a mesenchymal phenotype. This change
from epithelial to the mesenchymal phenotype of cancer cells makes it diffi cult to understand the mechanism underlying cancer
biology and tumor progression. A number of transcription factors involved in tumor cell EMT and microRNA-regulated EMT
have been reported. This review discussed recent fi ndings and new players in EMT in gastrointestinal cancers. Since the molecular
mechanisms of tumor progression are sometimes context-dependent, the recent fi ndings of EMT have been reviewed in a
context-dependent manner.
Key words: Epithelial-mesenchymal transition, gastrointestinal cancer, microRNA, transcription factor

Introduction Esophageal Cancer

Epithielial-mesenchymal transition (EMT) is a well-known Esophageal cancer ( EC) has two distinct histological
phenotype and essential for tumor invasion and subtypes, that is, esophageal squamous cell carcinoma
metastasis. [1-3] The phenotype change in EMT is drastic, so (ESCC) and esophageal adenocarcinoma (EAC). The
[4]
the theory has fascinated many investigators, and several former commonly occurs in Asia, whereas the latter is
mechanisms have been reported to date. However, the common in the United States and Western countries.
number of factors essential for EMT is increasing; thus, Transforming growth factor-β1 (TGF-β1) was reported
it is challenging to integrate those factors to understand to induce EMT in EAC via the mothers against
their networking. In this review, we briefl y updated the decapentaplegic homolog (SMAD) 4 pathway and
recent EMT fi ndings in a context-dependent manner, this signaling was inhibited by bone morphogenetic
because the mechanisms underlying a disease substantially protein 7, another member of the TGF-β1 superfamily.
[5]
depend on the original function of the affected organ. Using immortalized esophageal keratinocyte, TGF-β1
Theoretically, the concept of EMT explains various cancer was shown to regulate mitochondrial superoxide
characteristics including tumor cell invasion, metastasis, dismutase 2 (SOD2) which possesses antioxidant
chemo resistance and stem cell phenotype; therefore, it activity, to convert CD44 to CD44 cells. Expression
has considerable clinical signifi cance. Thus, this review of SOD2 was transcriptionally regulated by NF-κB and
low
high
explores both the molecular mechanism of EMT and its zinc fi nger E-box binding homeobox 2 (ZEB2), but
clinical signifi cance.
not ZEB1. In the same cells, it was also reported
[6]
Although many EMT players, such as transcription factors that TGF-β1-mediated EMT required p53 mutation
and microRNAs (miRNAs) have been introduced so far accompanied by up-regulation of ZEB1 and the loss
such as transcription factors and miRNAs, their roles are of epithelial growth factor receptor (EGFR)-dependent
to some extent-dependent on the context. Therefore, we
discussed the role of each molecule in a context-dependent This is an open access article distributed under the terms of the Creative
manner to clarify the specifi c role of each player. Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as
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Website:
www.jcmtjournal.com
How to cite this article: Okabe H, Mima K, Saito S, Hayashi H,
Imai K, Nitta H, Hashimoto D, Chikamoto A, Ishiko T, Beppu T, Baba H.
Epithelial-mesenchymal transition in gastroenterological cancer. J
DOI: Cancer Metastasis Treat 2015;1:183-9.
10.4103/2394-4722.165118
Received: 27-07-2015; Accepted: 12-08-2015.

© 2015 Journal of Cancer Metastasis and Treatment ¦ Published by Wolters Kluwer - Medknow 183