Journal article
E2F1 and E2F7 differentially regulate KPNA2 to promote the development of gallbladder cancer
Oncogene, v 38(8), pp 1269-1281
Feb 2019
PMID: 30254209
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Karyopherin alpha 2 (KPNA2) is a nuclear import factor that is elevated in multiple cancers. However, its molecular regulation at the transcriptional levels is poorly understood. Here we found that KPNA2 was significantly upregulated in gallbladder cancer (GBC), and the increased levels were correlated with short survival of patients. Gene knocking down of KPNA2 inhibited tumor cell proliferation and migration in vitro as well as xenografted tumor development in vivo. A typical transcription factor E2F1 associated with its DNA-binding partner DP1 bond to the promoter region of KPNA2 and induced KPNA2 expression. In contrast, an atypical transcription factor E2F7 competed against DP1 and blocked E2F1-induced KPNA2 gene activation. Mutation of the dimerization residues of E2F7 or DNA-binding domain of E2F1 abolished the suppressive effects of E2F7 on KPNA2 gene expression. In addition, KPNA2 mediated nuclear localization of E2F1 and E2F7, where they in turn controlled KPNA2 expression. Taken together, our data provided mechanistic insights into divergently transcriptional regulation of KPNA2, thus pointing to KPNA2 as a potential target for cancer therapy.
Metrics
Details
- Title
- E2F1 and E2F7 differentially regulate KPNA2 to promote the development of gallbladder cancer
- Creators
- Shanshan Xiang - XinHua HospitalZheng Wang - XinHua HospitalYuanyuan Ye - XinHua HospitalFei Zhang - XinHua HospitalHuaifeng Li - XinHua HospitalYang Yang - XinHua HospitalHuijie Miao - XinHua HospitalHaibin Liang - XinHua HospitalYijian Zhang - XinHua HospitalLin Jiang - XinHua HospitalYunping Hu - XinHua HospitalLei Zheng - Johns Hopkins MedicineXiyong Liu - Department of Molecular Pharmacology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.Yingbin Liu - XinHua HospitalHualou Liang - School of Biomedical Engineering, Science, and Health Systems (1997-)
- Publication Details
- Oncogene, v 38(8), pp 1269-1281
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000459249800009
- Scopus ID
- 2-s2.0-85053816988
- Other Identifier
- 991019320404604721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Genetics & Heredity
- Oncology