2. Academic Validation
  3. Targeting the interaction between RNA-binding protein HuR and FOXQ1 suppresses breast cancer invasion and metastasis

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

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].
PMID: 32332873 DOI: 10.1038/s42003-020-0933-1
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-134601
    98.91%, Hu Antigen R Inhibitor
    HuR