Sox2 is associated with cancer stem-like properties in colorectal cancer

Koki Takeda; Tsunekazu Mizushima; Yuhki Yokoyama; Haruka Hirose; Xin Wu; Yamin Qian; Katsuya Ikehata; Norikatsu Miyoshi; Hidekazu Takahashi; Naotsugu Haraguchi; Taishi Hata; Chu Matsuda; Yuichiro Doki; Masaki Mori; Hirofumi Yamamoto

doi:10.1038/s41598-018-36251-0

Sox2 is associated with cancer stem-like properties in colorectal cancer

Koki Takeda, Tsunekazu Mizushima, Yuhki Yokoyama, Haruka Hirose, Xin Wu, Yamin Qian, Katsuya Ikehata, Norikatsu Miyoshi, Hidekazu Takahashi, Naotsugu Haraguchi, Taishi Hata, Chu Matsuda, Yuichiro Doki, Masaki Mori, Hirofumi Yamamoto

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Abstract

Sox2 is known as the undifferentiated cell marker. Recent studies have shown that Sox2 may also be involved in the maintenance of cancer stem cells (CSCs) in skin and bladder cancers. In this study, we aimed to clarify the role of Sox2 in colorectal CSCs. Sox2 expression was measured in colon cancer cells and colorectal clinical samples by qRT-PCR and western blot analysis. To visualize the active Sox2 mRNA production, we generated a Sox2 promoter-dependent DsRed fluorescence emission system. Colon cancer cell lines and colorectal tumor tissues generally expressed the Sox2 protein. Knockdown of Sox2 by siRNA led to increased proliferative activity in Caco2 cells. Kaplan-Meier survival curves showed that the group with high Sox2 mRNA expression had a worse prognosis for relapse-free survival (RFS) than the low expression group (P = 0.045, median follow-up 60.0 months). Time-lapse image analysis revealed that most DsRed⁺ cells exhibited typical asymmetric cell division and had higher CSC marker expressions. The DsRed⁺ cells exhibited chemoresistance and they grew slower in vitro, yet they established rather larger tumors in vivo. Our data suggest that Sox2 may be a potential biomarker for colorectal CSCs.

Original language	English
Article number	17639
Journal	Scientific reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-36251-0
Publication status	Published - Dec 1 2018
Externally published	Yes

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10.1038/s41598-018-36251-0

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title = "Sox2 is associated with cancer stem-like properties in colorectal cancer",

abstract = "Sox2 is known as the undifferentiated cell marker. Recent studies have shown that Sox2 may also be involved in the maintenance of cancer stem cells (CSCs) in skin and bladder cancers. In this study, we aimed to clarify the role of Sox2 in colorectal CSCs. Sox2 expression was measured in colon cancer cells and colorectal clinical samples by qRT-PCR and western blot analysis. To visualize the active Sox2 mRNA production, we generated a Sox2 promoter-dependent DsRed fluorescence emission system. Colon cancer cell lines and colorectal tumor tissues generally expressed the Sox2 protein. Knockdown of Sox2 by siRNA led to increased proliferative activity in Caco2 cells. Kaplan-Meier survival curves showed that the group with high Sox2 mRNA expression had a worse prognosis for relapse-free survival (RFS) than the low expression group (P = 0.045, median follow-up 60.0 months). Time-lapse image analysis revealed that most DsRed+ cells exhibited typical asymmetric cell division and had higher CSC marker expressions. The DsRed+ cells exhibited chemoresistance and they grew slower in vitro, yet they established rather larger tumors in vivo. Our data suggest that Sox2 may be a potential biomarker for colorectal CSCs.",

author = "Koki Takeda and Tsunekazu Mizushima and Yuhki Yokoyama and Haruka Hirose and Xin Wu and Yamin Qian and Katsuya Ikehata and Norikatsu Miyoshi and Hidekazu Takahashi and Naotsugu Haraguchi and Taishi Hata and Chu Matsuda and Yuichiro Doki and Masaki Mori and Hirofumi Yamamoto",

note = "Funding Information: This work was supported by a grant from Kagoshima Shinsangyo Sousei Investment Limited Partnership (its general partner is Kagoshima Development Co., Ltd). Publisher Copyright: {\textcopyright} 2018, The Author(s). Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",

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doi = "10.1038/s41598-018-36251-0",

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T1 - Sox2 is associated with cancer stem-like properties in colorectal cancer

AU - Takeda, Koki

AU - Mizushima, Tsunekazu

AU - Yokoyama, Yuhki

AU - Hirose, Haruka

AU - Wu, Xin

AU - Qian, Yamin

AU - Ikehata, Katsuya

AU - Miyoshi, Norikatsu

AU - Takahashi, Hidekazu

AU - Haraguchi, Naotsugu

AU - Hata, Taishi

AU - Matsuda, Chu

AU - Doki, Yuichiro

AU - Mori, Masaki

AU - Yamamoto, Hirofumi

N1 - Funding Information: This work was supported by a grant from Kagoshima Shinsangyo Sousei Investment Limited Partnership (its general partner is Kagoshima Development Co., Ltd). Publisher Copyright: © 2018, The Author(s). Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Sox2 is known as the undifferentiated cell marker. Recent studies have shown that Sox2 may also be involved in the maintenance of cancer stem cells (CSCs) in skin and bladder cancers. In this study, we aimed to clarify the role of Sox2 in colorectal CSCs. Sox2 expression was measured in colon cancer cells and colorectal clinical samples by qRT-PCR and western blot analysis. To visualize the active Sox2 mRNA production, we generated a Sox2 promoter-dependent DsRed fluorescence emission system. Colon cancer cell lines and colorectal tumor tissues generally expressed the Sox2 protein. Knockdown of Sox2 by siRNA led to increased proliferative activity in Caco2 cells. Kaplan-Meier survival curves showed that the group with high Sox2 mRNA expression had a worse prognosis for relapse-free survival (RFS) than the low expression group (P = 0.045, median follow-up 60.0 months). Time-lapse image analysis revealed that most DsRed+ cells exhibited typical asymmetric cell division and had higher CSC marker expressions. The DsRed+ cells exhibited chemoresistance and they grew slower in vitro, yet they established rather larger tumors in vivo. Our data suggest that Sox2 may be a potential biomarker for colorectal CSCs.

AB - Sox2 is known as the undifferentiated cell marker. Recent studies have shown that Sox2 may also be involved in the maintenance of cancer stem cells (CSCs) in skin and bladder cancers. In this study, we aimed to clarify the role of Sox2 in colorectal CSCs. Sox2 expression was measured in colon cancer cells and colorectal clinical samples by qRT-PCR and western blot analysis. To visualize the active Sox2 mRNA production, we generated a Sox2 promoter-dependent DsRed fluorescence emission system. Colon cancer cell lines and colorectal tumor tissues generally expressed the Sox2 protein. Knockdown of Sox2 by siRNA led to increased proliferative activity in Caco2 cells. Kaplan-Meier survival curves showed that the group with high Sox2 mRNA expression had a worse prognosis for relapse-free survival (RFS) than the low expression group (P = 0.045, median follow-up 60.0 months). Time-lapse image analysis revealed that most DsRed+ cells exhibited typical asymmetric cell division and had higher CSC marker expressions. The DsRed+ cells exhibited chemoresistance and they grew slower in vitro, yet they established rather larger tumors in vivo. Our data suggest that Sox2 may be a potential biomarker for colorectal CSCs.

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Sox2 is associated with cancer stem-like properties in colorectal cancer

Abstract

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