IL-6/STAT3/TWIST inhibition reverses ionizing radiation-induced EMT and radioresistance in esophageal squamous carcinoma

// Chunbao Zang 1, * , Xujie Liu 1, * , Bing Li 2, * , Yanqiong He 1 , Shen Jing 1 , Yujia He 1 , Wenli Wu 1 , Bingqian Zhang 1 , Shuhong Ma 1 , Weiwei Dai 1 , Shaolin Li 1 , Zhiping Peng 1 1 Department of Radiological Medicine, Chongqing Medical University, Chonging, China 2 Department of Otorhinolaryngology, The First Affiliated Hospital of Chonqqing Medical University, Chongqing, China * These authors contributed equally to this work Correspondence to: Zhiping Peng, email: pengzhiping@cqmu.edu.cn Keywords: radioresistance, EMT, IL-6/STAT3/TWIST pathway Received: July 25, 2016      Accepted: December 27, 2016      Published: January 04, 2017 ABSTRACT The acquisition of radioresistance by esophageal squamous carcinoma (ESC) cells during radiotherapy may lead to cancer recurrence and poor survival. Previous studies have demonstrated that ionizing radiation (IR) induces epithelial–mesenchymal transition (EMT) of ESC cells accompanied by increased migration, invasion, and radioresistance. However, the underlying molecular mechanisms of IR-induced EMT and radioresistance are not well established, hampering the development of potential solutions. To address this issue, we investigated the role of the IL-6/STAT3/TWIST signaling pathway in IR-induced EMT. We found not only the pathway was activated during IR-induced EMT but also STAT3 inhibition or Twist depletion reversed the EMT process and attenuated radioresistance. These results improve our understanding of the underlying mechanisms involved in IR-induced EMT and suggest potential interventions to prevent EMT-induced acquisition of radioresistance.