FOXP3 inhibits cancer stem cell self-renewal via transcriptional repression of COX2 in colorectal cancer cells.

Shuo Liu,Xianghui Xing,Yuan Gao,Weina Li,Xiaochang Xue,Cun Zhang,Qiang Hao,Kuo Zhang,Yingqi Zhang,Xiaoju Li,Zhaowei Wang,Wei Zhang,Meng Li,Guang Cheng,Shuning Wang

doi:10.18632/oncotarget.17974

Shuo Liu, Xianghui Xing + Show 13 more

Open Access

https://doi.org/10.18632/oncotarget.17974

Copy DOI

Journal: Oncotarget	Publication Date: May 18, 2017
Citations: 20	License type: cc-by

Affiliation: Air Force Medical University

Abstract

Colon cancer stem cell (cCSC) is considered as the seed cell of colon cancer initiation and metastasis. Cyclooxygenase-2 (COX2), a downstream target of NFκB, is found to be essential in promoting cancer stem cell renewal. However, how COX2 is dysregulated in cCSCs is largely unknown. In this study, we found that the expression of transcription factor FOXP3 was much lower in the spheroids than that in the parental tumor cells. Overexpression of FOXP3 significantly decreased the numbers of spheres, reduced the side population. Accordingly, FOXP3 expression decreased the tumor size and weight in the xenograft model. The tumor inhibitory effects of FOXP3 were rarely seen when COX2 was additionally knocked down. Mechanically, FOXP3 transcriptionally repressed COX2 expression via interacting with and thus inhibiting p65 activity on the putative NFκB response elements in COX2 promoter. Taken together, we here revealed possible involvement of FOXP3 in regulating cCSC self-renewal via tuning COX2 expression, and thus providing a new target for the eradication of colon cancer stem cells.

Highlights

IntroductionIn the last several years, evidence has suggested that the capacity of initiating a tumor could be rather a unique characteristic of cells with stemness properties and the existence of colon cancer stem cells have been identified [1]
Colorectal cancer is one of the most frequent occurred cancers in the world
All of these data indicate that FOXP3 and COX2 might involve in the regulation of the stemness of colon cancer stem cells

Summary

Introduction

In the last several years, evidence has suggested that the capacity of initiating a tumor could be rather a unique characteristic of cells with stemness properties and the existence of colon cancer stem cells have been identified [1]. These so-called CSCs were originally identified through the expression of the CD133 glycoprotein using an antibody directed to its epitope AC133. In addition to initiating and sustaining tumor growth, cCSCs are considered as the seed cell for chemoresistance and metastasis [2]. Eradication of the cCSCs is believed to be the key to the treatment of colorectal cancer

Methods

Results

Conclusion