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STAT1 inhibits STAT3 activation in esophageal squamous cell carcinoma

Authors Liu Z, Zhang Y, Chen Y, Lin Y, Lin Z, Wang H

Received 31 July 2018

Accepted for publication 4 November 2018

Published 29 November 2018 Volume 2018:10 Pages 6517—6523


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Harikrishna Nakshatri

Zhaoyong Liu,1,* Ying Zhang,2,* Yelong Chen,1 Youbin Lin,1 Zhen Lin,2 Hu Wang1

1Department of Orthopaedics, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China; 2Department of Pathology, Shantou University Medical College, Shantou, Guangdong, China

*These authors contributed equally to this work

Background: Signal transducer and activator of transcription (STAT) 1 is an important transcription factor and has been reported to be a tumor suppressor in many types of cancer. However, another STAT family member, STAT3, is considered to be an oncogene. The cross-talk between STAT1 and STAT3 in cancer has not been fully demonstrated.
Materials and methods: Esophageal squamous cell carcinoma (ESCC) was used as a model to examine STAT1-STAT3 cross-regulation in cancer. We detected STAT1-STAT3 binding by co-immunoprecipitation (co-IP) and measured the transcription activity by using a luciferase reporter gene. DNA binding was detected by a DNA probe. Expression of STAT1 and STAT3 in ESCC was detected by immunohistochemistry.
Results: We found that STAT1 attenuated STAT3 activity upon oncostatin M treatment by decreasing STAT3 transcription activity and DNA binding ability of STAT3. Furthermore STAT3 downregulation increased the phosphorylation and transcriptional activation of STAT1. Finally, STAT1 expression and STAT3 expression were negatively correlated in ESCC cases.
Conclusion: Altogether, this paper demonstrated STAT1 and STAT3 cross-regulation in ESCC and proposed that STAT3 downregulation and/or STAT1 accumulation may be a therapeutic approach to treat ESCC.

Keywords: STAT1, STAT3, esophageal squamous cell carcinoma, transcription activity

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