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Targeting the interaction between RNA-binding protein HuR and FOXQ1 suppresses breast cancer invasion and metastasis
Wu, Xiaoqing Gardashova, Gulhumay Lan, Lan Han, Shuang Zhong, Cuncong Marquez, Rebecca T. Wei, Lanjing Wood, Spencer Roy, Sudeshna Gowthaman, Ragul
Wu, Xiaoqing
Gardashova, Gulhumay
Lan, Lan
Han, Shuang
Zhong, Cuncong
Marquez, Rebecca T.
Wei, Lanjing
Wood, Spencer
Roy, Sudeshna
Gowthaman, Ragul
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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.
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This work is licensed under a Creative Commons Attribution 4.0 International License.
Date
2020-04-24
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Publisher
Nature Research
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Keywords
Drug development, Target validation, Breast cancer, Metastasis
Citation
Wu, X., Gardashova, G., Lan, L., Han, S., Zhong, C., Marquez, R. T., Wei, L., Wood, S., Roy, S., Gowthaman, R., Karanicolas, J., Gao, F. P., Dixon, D. A., Welch, D. R., Li, L., Ji, M., Aubé, J., & Xu, L. (2020). Targeting the interaction between RNA-binding protein HuR and FOXQ1 suppresses breast cancer invasion and metastasis. Communications biology, 3(1), 193. https://doi.org/10.1038/s42003-020-0933-1