Thioredoxin 1 upregulates FOXO1 transcriptional activity in drug resistance in ovarian cancer cells

Jianlin Wang; Hao Yang; Wenjie Li; Huibi Xu; Xiangliang Yang; Lu Gan

doi:10.1016/j.bbadis.2014.12.002

Thioredoxin 1 upregulates FOXO1 transcriptional activity in drug resistance in ovarian cancer cells

Biochim Biophys Acta. 2015 Mar;1852(3):395-405. doi: 10.1016/j.bbadis.2014.12.002. Epub 2014 Dec 5.

Authors

Jianlin Wang¹, Hao Yang¹, Wenjie Li¹, Huibi Xu¹, Xiangliang Yang¹, Lu Gan²

Affiliations

¹ 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.
² 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.

PMID: 25483711
DOI: 10.1016/j.bbadis.2014.12.002

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.

Keywords: Drug resistance; FOXO1; Ovarian cancer cells; ROS; Trx1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Substitution
Antineoplastic Agents, Phytogenic / pharmacology
Cell Line, Tumor
Drug Resistance, Neoplasm*
Female
Forkhead Box Protein O1
Forkhead Transcription Factors / genetics
Forkhead Transcription Factors / metabolism*
Humans
Mutation, Missense
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Ovarian Neoplasms / drug therapy
Ovarian Neoplasms / genetics
Ovarian Neoplasms / metabolism*
Ovarian Neoplasms / pathology
Paclitaxel / pharmacology
Reactive Oxygen Species
Signal Transduction*
Thioredoxins / genetics
Thioredoxins / metabolism*
Transcriptional Activation*

Substances

Antineoplastic Agents, Phytogenic
FOXO1 protein, human
Forkhead Box Protein O1
Forkhead Transcription Factors
Neoplasm Proteins
Reactive Oxygen Species
Thioredoxins
Paclitaxel