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.

Highlights

  • Sox[2] is known as the undifferentiated cell marker

  • Zhu et al demonstrated that Sox2-expressing bladder cancer cells express high levels of cancer stem cells (CSCs) markers keratin[14] (KRT14) and CD44v6, and that ablation of Sox2-expressing cells leads to tumor regression[16]

  • We found that colon cancer cells express considerable levels of the Sox[2] protein, comparable to the MCF7 and U87 cells used as positive controls

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Summary

Introduction

Sox[2] is known as the undifferentiated cell marker. Recent studies have shown that Sox[2] may be involved in the maintenance of cancer stem cells (CSCs) in skin and bladder cancers. Zhu et al demonstrated that Sox2-expressing bladder cancer cells express high levels of CSC markers keratin[14] (KRT14) and CD44v6, and that ablation of Sox2-expressing cells leads to tumor regression[16]. These findings suggest that Sox[2] may be one of the key molecules driving CSCs in skin and bladder carcinomas[15,16]. : not significant resistance to chemotherapy and asymmetric cell division[19] To monitor these cells, we constructed a fluorescence cell visualization system in response to Sox[2] promoter activation and tried to elucidate whether Sox[2] may drive CSCs in colon cancer

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