E‑cadherin regulates proliferation of colorectal cancer stem cells through NANOG

Tamura,Shingo; Isobe,Taichi; Ariyama,Hiroshi; Nakano,Michitaka; Kikushige,Yoshikane; Takaishi,Shigeo; Kusaba,Hitoshi; Takenaka,Katsuto; Ueki,Takashi; Nakamura,Masafumi; Akashi,Koichi; Baba,Eishi

doi:10.3892/or.2018.6464

E‑cadherin regulates proliferation of colorectal cancer stem cells through NANOG

Authors:
- Shingo Tamura
- Taichi Isobe
- Hiroshi Ariyama
- Michitaka Nakano
- Yoshikane Kikushige
- Shigeo Takaishi
- Hitoshi Kusaba
- Katsuto Takenaka
- Takashi Ueki
- Masafumi Nakamura
- Koichi Akashi
- Eishi Baba
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Affiliations: Department of Medicine, Kyushu University, Fukuoka 812‑8582, Japan, Department of Comprehensive Clinical Oncology, Faculty of Medical Sciences, Kyushu University, Fukuoka 812‑8582, Japan, Department of Surgery and Oncology, Kyushu University, Fukuoka 812‑8582, Japan
Published online on: May 24, 2018 https://doi.org/10.3892/or.2018.6464
Pages: 693-703
Copyright: © Tamura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cancer stem cells (CSCs) possess a self‑renewal ability and display tumorigenic potential in immunodeficient mice. Colorectal CSCs are thought to be a uniform population and no functionally distinct subpopulations have been identified. Because E‑cadherin is an essential molecule for self‑renewal of embryonic stem cells, we examined E‑cadherin expression, which may play a role in maintaining the properties of CSCs, in EpCAMhigh/CD44+ colorectal CSCs from human primary colorectal cancers. We obtained 18 surgical specimens of human primary colorectal cancer. CD44, EpCAM, and E‑cadherin expression were analyzed by fluorescence‑activated cell sorting. Sorted EpCAMhigh/CD44+ colorectal CSCs were injected into immunodeficient mice to estimate the tumorigenic potential. Genetic profiles were analyzed by cDNA microarray. Notably, colorectal CSCs could be divided into two populations based on the E‑cadherin expression status, and they exhibited different pathological characteristics. Compared to E‑cadherin‑negative colorectal CSCs, E‑cadherin‑positive (EC+) colorectal CSCs demonstrated higher tumor growth potential in vivo. EC+ colorectal CSCs revealed a higher expression of the pluripotency factor NANOG, which contributed to the higher tumor growth potential of EC+ colorectal CSCs through control of cyclin D1 expression. These findings are the first demonstration of functionally distinct subpopulations of colorectal CSCs in human clinical samples.

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