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Title: Multiple roles of single-minded 2 in esophageal squamous cell carcinoma and its clinical implications
Authors: Tamaoki, Masashi
Komatsuzaki, Rie
Komatsu, Masayuki
Minashi, Keiko
Aoyagi, Kazuhiko
Nishimura, Takao
Chiwaki, Fumiko
Hiroki, Tomoko
Daiko, Hiroyuki
Morishita, Kazuhiro
Sakai, Yoshiharu
Seno, Hiroshi  kyouindb  KAKEN_id
Chiba, Tsutomu
Muto, Manabu  kyouindb  KAKEN_id
Yoshida, Teruhiko
Sasaki, Hiroki
Author's alias: 坂井, 義治
妹尾, 浩
千葉, 勉
武藤, 学
Keywords: ARNT
esophageal squamous cell carcinoma
Issue Date: Apr-2018
Publisher: Wiley
Journal title: Cancer Science
Volume: 109
Issue: 4
Start page: 1121
End page: 1134
Abstract: Degree of histological differentiation is an important characteristic of cancers and may be associated with malignant potential. However, in squamous cell carcinomas, a key transcriptional factor regulating tumor differentiation is largely unknown. Chemoradiotherapy (CRT) is a standard treatment for locally advanced esophageal squamous cell carcinoma; however, the survival rate is still below 40%. From microarray data, single‐minded 2 (SIM2) was overexpressed in the epithelial subtype. Here, we investigated the correlation between SIM2 expression and its clinical implication, and in vitro and in vivo functions of SIM2 in tumor differentiation and in CRT sensitivity. Although SIM2 was suppressed in cancerous tissues, SIM2‐high ESCC showed a favorable prognosis in CRT. Transient SIM2 expression followed by 3D culture induced expression of differentiation markers and suppressed epithelial‐mesenchymal transition‐ and basal‐cell markers. Levels of PDPN‐high tumor basal cells and of expression of genes for DNA repair and antioxidant enzymes were reduced in stable transfectants, and they showed high CDDP and H2O2 sensitivities, and their xenografts showed a well‐differentiated histology. Reduction of tumor basal cells was restored by knockdown of aryl hydrocarbon receptor nuclear translocator (ARNT) that interacted with SIM2. Together, SIM2 increases CRT sensitivity through tumor differentiation by cooperation with ARNT.
Rights: © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
DOI(Published Version): 10.1111/cas.13531
PubMed ID: 29427302
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