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

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

doi:10.18632/oncotarget.17974

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Research Papers:

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

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

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Oncotarget. 2017; 8:44694-44704. https://doi.org/10.18632/oncotarget.17974

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Abstract

Shuo Liu1,*, Cun Zhang1,*, Kuo Zhang1,*, Yuan Gao1, Zhaowei Wang1, Xiaoju Li1, Guang Cheng4, Shuning Wang1, Xiaochang Xue1, Weina Li1, Wei Zhang1, Yingqi Zhang1, Xianghui Xing3, Meng Li2 and Qiang Hao1

1The State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an 710032, China

2Department of Pharmacogenomics, School of Pharmacy, The Fourth Military Medical University, Xi'an 710032, China

3State Key Laboratory of Military Stomatology, Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China

4Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China

*These authors have contributed equally to this work

Correspondence to:

Qiang Hao, email: [email protected]

Meng Li, email: [email protected]

Xianghui Xing, email: [email protected]

Keywords: FOXP3, COX2, NFκB, cancer stem cell, transcriptional regulation

Received: January 12, 2017 Accepted: April 25, 2017 Published: May 18, 2017

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.

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Research Papers:

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

Abstract