Targeting uPAR by CRISPR/Cas9 System Attenuates Cancer Malignancy and Multidrug Resistance

Front Oncol. 2019 Feb 27:9:80. doi: 10.3389/fonc.2019.00080. eCollection 2019.

Abstract

Urokinase plasminogen activator receptor (uPAR), a member of the lymphocyte antigen 6 protein superfamily, is overexpressed in different types of cancers and plays an important role in tumorigenesis and development. In this study, we successfully targeted uPAR by CRISPR/Cas9 system in two human cancer cell lines with two individual sgRNAs. Knockout of uPAR inhibited cell proliferation, migration and invasion. Furthermore, knockout of uPAR decreases resistance to 5-FU, cisplatin, docetaxel, and doxorubicin in these cells. Although there are several limitations in the application of CRISPR/Cas9 system for cancer patients, our study offers valuable evidences for the role of uPAR in cancer malignancy and drug resistance.

Keywords: CRISPR/Cas9; cancer; drug resistance; malignancy; uPAR.