title: Stemness and chemotherapeutic drug resistance induced by EIF5A2 overexpression in esophageal squamous cell carcinoma.
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.
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.|Guangdong Esophageal Cancer Institute, Guangzhou, China.
authors: Hong
authors: H
authors: Yang
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.|Guangdong Esophageal Cancer Institute, Guangzhou, China.
authors: Xiao-dong
authors: XD
authors: Li
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Ying
authors: Y
authors: Zhou
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Xiaojiao
authors: X
authors: Ban
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Ting-ting
authors: TT
authors: Zeng
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Lei
authors: L
authors: Li
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Bao-zhu
authors: BZ
authors: Zhang
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Jingping
authors: J
authors: Yun
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Dan
authors: D
authors: Xie
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.|Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China.
authors: Xin-Yuan
authors: XY
authors: Guan
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Yan
authors: Y
authors: Li
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D010448:Peptide Initiation Factors / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043823:Taxoids / Q000494:pharmacology; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D000970:Antineoplastic Agents; D000077143:Docetaxel; D005472:Fluorouracil; D017239:Paclitaxel; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D043823:Taxoids; D000097574:Eukaryotic Translation Initiation Factor 5A
keywords: EIF5A2; chemoresistance; esophageal squamous cell carcinoma (ESCC); stemness