Targeting the interaction between RNA-binding protein HuR and FOXQ1 suppresses breast cancer invasion and metastasis PMID: 32332873

ADC Targets in Oncology

2026-04-10

Targeting the interaction between RNA-binding protein HuR and FOXQ1 suppresses breast cancer invasion and metastasis

Commun Biol. 2020 Apr 24;3(1):193. doi: 10.1038/s42003-020-0933-1.

Xiaoqing Wu ¹ ² , Gulhumay Gardashova ¹ , Lan Lan ¹ , Shuang Han ¹ , Cuncong Zhong ³ , Rebecca T Marquez ¹ , Lanjing Wei ⁴ , Spencer Wood ⁵ , Sudeshna Roy ⁵ ⁶ , Ragul Gowthaman ⁷ , John Karanicolas ⁸ , Fei P Gao ⁹ , Dan A Dixon ¹ ² , Danny R Welch ² ¹⁰ , Ling Li ¹¹ , Min Ji ¹² , Jeffrey Aubé ⁵ , Liang Xu ¹³ ¹⁴ ¹⁵

Affiliations

1. Department of Molecular Biosciences, The University of Kansas, Lawrence, KS, USA.
2. The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS, USA.
3. Department of Electrical Engineering and Computer Science, The University of Kansas, Lawrence, KS, USA.
4. Bioengineering Program, The University of Kansas, Lawrence, KS, USA.
5. Department of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, The University of North Carolina, Chapel Hill, NC, USA.
6. Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, USA.
7. Center for Computational Biology, The University of Kansas, Lawrence, KS, USA.
8. Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA, USA.
9. Protein Production Group, NIH COBRE in Protein Structure and Function, The University of Kansas, Lawrence, KS, USA.
10. Department of Cancer Biology, The University of Kansas Medical Center, Kansas City, KS, USA.
11. National Translational Science Center for Molecular Medicine, Department of Cell Biology, School of Basic Medicine, The Air Force Medical University, Xi'an, Shanxi, China.
12. School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, China.
13. Department of Molecular Biosciences, The University of Kansas, Lawrence, KS, USA. [email protected].
14. The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS, USA. [email protected].
15. Department of Radiation Oncology, The University of Kansas Medical Center, Kansas City, KS, USA. [email protected].

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.