Nature Communications (Dec 2018)
Targeting the BRD4/FOXO3a/CDK6 axis sensitizes AKT inhibition in luminal breast cancer
- Jingyi Liu,
- Zhibing Duan,
- Weijie Guo,
- Lei Zeng,
- Yadi Wu,
- Yule Chen,
- Fang Tai,
- Yifan Wang,
- Yiwei Lin,
- Qiang Zhang,
- Yanling He,
- Jiong Deng,
- Rachel L. Stewart,
- Chi Wang,
- Pengnian Charles Lin,
- Saghi Ghaffari,
- B. Mark Evers,
- Suling Liu,
- Ming-Ming Zhou,
- Binhua P. Zhou,
- Jian Shi
Affiliations
- Jingyi Liu
- Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine
- Zhibing Duan
- Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine
- Weijie Guo
- Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine
- Lei Zeng
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai
- Yadi Wu
- Markey Cancer Center, University of Kentucky College of Medicine
- Yule Chen
- Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine
- Fang Tai
- Department of Pathology, School of Basic Medical Sciences, Southern Medical University
- Yifan Wang
- Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine
- Yiwei Lin
- Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine
- Qiang Zhang
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai
- Yanling He
- Department of Pathology, School of Basic Medical Sciences, Southern Medical University
- Jiong Deng
- Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine
- Rachel L. Stewart
- Markey Cancer Center, University of Kentucky College of Medicine
- Chi Wang
- Markey Cancer Center, University of Kentucky College of Medicine
- Pengnian Charles Lin
- Center for Cancer Research, National Cancer Institute-Frederick
- Saghi Ghaffari
- Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai
- B. Mark Evers
- Markey Cancer Center, University of Kentucky College of Medicine
- Suling Liu
- Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Cancer Institute, Fudan University Shanghai Cancer Center
- Ming-Ming Zhou
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai
- Binhua P. Zhou
- Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine
- Jian Shi
- Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine
- DOI
- https://doi.org/10.1038/s41467-018-07258-y
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 17
Abstract
The molecular mechanism underlying the resistance of AKT inhibitors in breast cancer is still elusive. Here, the authors demonstrate that BRD4/FOXO3a axis upregulates CDK6 promoter activity to promote resistance to AKT inhibition in breast cancer cells and that blocking the action of CDK6 re-sensitizes resistant cancer cells to growth inhibition.
