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

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.

• Authors: Shuo Liu, Cun Zhang, Kuo 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
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 27 Pg. 44694-44704 (Jul 04 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28591725 (Publication Type: Journal Article)

Chemical References

• FOXP3 protein, human
• Forkhead Transcription Factors
• NF-kappa B
• Cyclooxygenase 2

Topics

• Animals
• Cell Line, Tumor
• Cell Self Renewal (genetics)
• Colorectal Neoplasms (genetics, metabolism, pathology)
• Cyclooxygenase 2 (genetics, metabolism)
• Disease Models, Animal
• Forkhead Transcription Factors (genetics, metabolism)
• Gene Expression Regulation
• Gene Expression Regulation, Neoplastic
• Heterografts
• Humans
• Mice
• NF-kappa B (metabolism)
• Neoplastic Stem Cells (metabolism)
• Promoter Regions, Genetic
• Protein Binding
• Transcription, Genetic