title: Thioredoxin 1 upregulates FOXO1 transcriptional activity in drug resistance in ovarian cancer cells.
abstract: Drug resistance is the major cause of failure of cancer chemotherapy in ovarian cancer. However, the molecular mechanisms on the regulation of drug resistance are not fully understood. Here we showed that Trx1 and FOXO1 were involved in paclitaxel (PTX)-induced drug resistance in ovarian cancer A2780 cells. PTX induced reactive oxygen species (ROS) and resulted in Trx1 and FOXO1 nuclear translocation. We further found that Trx1 bound to FOXO1 and enhanced FOXO1 transcriptional activity; however Trx1 C69S mutant which is barely detected in the nucleus downregulated Trx1-FOXO1 interaction and Trx1-induced FOXO1 transcriptional activation. Silencing of FOXO1 abrogated Trx1-induced drug resistance. Trx1 increased FOXO1-induced drug resistance, while Trx1 C69S mutant completely abolished the regulation of FOXO1-mediated drug resistance by Trx1. These findings provided a novel mechanism on Trx1/FOXO1 signaling in drug resistance in ovarian cancer cells.
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Huibi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China. Electronic address: lugan@mail.hust.edu.cn.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
mesh_terms: D019943:Amino Acid Substitution; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D013879:Thioredoxins; D017239:Paclitaxel
keywords: Drug resistance; FOXO1; Ovarian cancer cells; ROS; Trx1