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NFATC2 is a novel therapeutic target for colorectal cancer stem cells

Authors Lang T, Ding X, Kong L, Zhou X, Zhang Z, Ju HX, Ding S

Received 23 March 2018

Accepted for publication 19 May 2018

Published 15 October 2018 Volume 2018:11 Pages 6911—6924

DOI https://doi.org/10.2147/OTT.S169129

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Samir Farghaly


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Tingyuan Lang,1 Xiaojuan Ding,1 Liangsheng Kong,1 Xiaoyan Zhou,1 Zhiqi Zhang,2 Huangxian Ju,1,3 Shijia Ding1

1Key Laboratory of Laboratory Medical Diagnostics (Ministry of Education of China), Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of China; 3State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, People’s Republic of China

Background: Colorectal cancer stem cells (CRC-SCs) contribute to the initiation and progression of colorectal cancer (CRC). However, the underlying mechanisms for the propagation of CRC-SCs have remained elusive.
Purpose: The objective of this study was to study the role of NFATC2 in maintenance of the stemness in CRC-SCs.
Method: The expression levels of mRNA and protein were determined by qRT-PCR and western-blot, respectively. CRC-SCs were isolated by spheroid formation assay and flowcytometry. The sphere-forming and self-renewal abilities of CRC-SCs were determined by spheroid formation assay. The tumorigenicity of CRC-SCs was determined by cell-derived xenograft model. Gene manipulation was performed by lentivirus-mediated delivery system.
Results: We first found that NFATC2 is upregulated in primary CRC-SCs. Overexpression of NFATC2 promotes self-renewal and the expression of stem cell markers of CRC-SCs. Conversely, knockdown of NFATC2 attenuates stem cell-like properties of CRC-SCs. Mecha­nistic analysis indicated that NFATC2 upregulates the expression of AJUBA, downregulates the phosphorylation level of YAP, and therefore activates the transcriptional activities of YAP and promotes the stemness of CRC-SCs.
Conclusion: Our findings demonstrate NFATC2 as an oncogene that can promote the stemness of CRC-SCs. This work suggests a novel therapeutic strategy against CRC caused by aberrant expression of NFATC2.

Keywords: NFATC2, colorectal cancer, stem cells, stemness, YAP

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