Targeting the interaction between RNA-binding protein HuR and FOXQ1 suppresses breast cancer invasion and metastasis
Abstract
Patients diagnosed with metastatic breast cancer have a dismal 5-year survival rate of only 24%. The RNA-binding protein Hu antigen R (HuR) is upregulated in breast cancer, and elevated cytoplasmic HuR correlates with high-grade tumors and poor clinical outcome of breast cancer. HuR promotes tumorigenesis by regulating numerous proto-oncogenes, growth factors, and cytokines that support major tumor hallmarks including invasion and metastasis. Here, we report a HuR inhibitor KH-3, which potently suppresses breast cancer cell growth and invasion. Furthermore, KH-3 inhibits breast cancer experimental lung metastasis, improves mouse survival, and reduces orthotopic tumor growth. Mechanistically, we identify FOXQ1 as a direct target of HuR. KH-3 disrupts HuR–FOXQ1 mRNA interaction, leading to inhibition of breast cancer invasion. Our study suggests that inhibiting HuR is a promising therapeutic strategy for lethal metastatic breast cancer.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 24, 2020
- Source ID
- 10.1038/s42003-020-0933-1
Entities
People
- Cuncong Zhong
- Dan A Dixon
- Danny R. Welch
- Fei P Gao
- Gulhumay Gardashova
- Jeffrey Aubé
- John Karanicolas
- Lan Lan
- Lanjing Wei
- Liang Xu
- Ling Li
- Min Ji
- Ragul Gowthaman
- Rebecca T. Marquez
- Shuang Han
- Spencer Wood
- Sudeshna Roy
- Xiaoqing Wu
Organizations
- Center for Information Technology
- Kansas Bioscience Authority
- National Cancer Institute
- National Foundation for Cancer Research
- Susan G. Komen for the Cure
- United States Department of Defense
- United States Department of Health and Human Services