STAT1 inhibits STAT3 activation in esophageal squamous cell carcinoma

• Published in: Cancer management and research Vol. 10; pp. 6517 - 6523
• Main Authors: Liu, Zhaoyong, Zhang, Ying, Chen, Yelong, Lin, Youbin, Lin, Zhen, Wang, Hu
• Format: Journal Article
• Language: English
• Published: New Zealand Taylor & Francis Ltd 01.01.2018; Dove Medical Press
• Subjects: Apoptosis; Cell growth; Cloning; Esophageal cancer; esophageal squamous cell carcinoma; Gene expression; Growth factors; Original Research; Proteins; Squamous cell carcinoma; STAT1; STAT3; transcription activity; Trends; United States > US; China; esophageal squamous cell carcinoma; STAT1; transcription activity; STAT3
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S182105

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. 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. 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. 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.