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

• DOI: 10.1038/s42003-020-0933-1
• Publication Date: 2020-04-24T10:26:38Z
• Authors: Xiaoqing Wu; Gulhumay Gardashova; Lan Lan; Shuang Han; Cuncong Zhong; Rebecca T. Marquez; Lanjing Wei; Spencer Wood; Sudeshna Roy; Ragul Gowthaman; John Karanicolas; Fei P. Gao; Dan A. Dixon; Danny R. Welch; Ling Li; Min Ji; Jeffrey Aubé; Liang Xu
• Keywords: 0301 basic medicine; 570; Lung Neoplasms; 610; Mice, Nude; Drug development; Antineoplastic Agents; Breast Neoplasms; Article; Target validation; Metastasis; ELAV-Like Protein 1; 03 medical and health sciences; Breast cancer; Cell Movement; Cell Line, Tumor; Animals; Humans; Neoplasm Invasiveness; Cell Proliferation; Mice, Inbred BALB C; 0303 health sciences; Forkhead Transcription Factors; Middle Aged; Xenograft Model Antitumor Assays; Tumor Burden; 3. Good health; Female; Signal Transduction

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 cancer, and elevated cytoplasmic HuR correlates high-grade tumors poor clinical outcome cancer. promotes tumorigenesis by regulating numerous proto-oncogenes, growth factors, cytokines that support major tumor hallmarks including invasion metastasis. Here, we report inhibitor KH-3, which potently suppresses cell invasion. Furthermore, KH-3 inhibits experimental lung metastasis, improves mouse survival, reduces orthotopic growth. Mechanistically, identify FOXQ1 as direct target HuR. disrupts HuR–FOXQ1 mRNA interaction, leading to inhibition Our study suggests inhibiting promising therapeutic strategy for lethal