Stemness and chemotherapeutic drug resistance induced by EIF5A2 overexpression in esophageal squamous cell carcinoma

// Hong Yang 1, 2 , Xiao-dong Li 1, 2 , Ying Zhou 1 , Xiaojiao Ban 1 , Ting-ting Zeng 1 , Lei Li 1 , Bao-zhu Zhang 1 , Jingping Yun 1 , Dan Xie 1 , Xin-Yuan Guan 1, 3 , Yan Li 1 1 Sun Yat-sen University Cancer Center, State key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China 2 Guangdong Esophageal Cancer Institute, Guangzhou, China 3 Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China Correspondence to: Yan Li, e-mail: liy6@mail.sysu.edu.cn Keywords: esophageal squamous cell carcinoma (ESCC), EIF5A2, stemness, chemoresistance Received: June 19, 2015 Accepted: July 08, 2015 Published: July 20, 2015 ABSTRACT Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies of the digestive tract in East Asian countries. Multimodal therapies, including adjuvant chemotherapy and neo-adjuvant chemotherapy, have become more often used for patients with advanced ESCC. However, the chemotherapy effect is often limited by patients’ drug resistance. This study demonstrated that EIF5A2 (eukaryotic translation initiation factor 5A2) overexpression induced stemness and chemoresistance in ESCC cells. We showed that EIF5A2 overexpression in ESCC cells resulted in increased chemoresistance to 5-fluorouracil (5-FU), docetaxel and taxol. In contrast, shRNAs suppressing eIF5A2 increased tumor sensitivity to these chemotherapeutic drugs. In addition, EIF5A2 overexpression was correlated with a poorer overall survival in patients with ESCC who underwent taxane-based chemotherapy after esophagectomy ( P < 0.05). Based on these results, we suggest that EIF5A2 could be a predictive biomarker for selecting appropriate chemo-treatment for ESCC patients and EIF5A2 inhibitors might be considered as combination therapy to enhance chemosensitivity in patients with ESCC.