Zhang Jinping, Zhang Shuman, Dörflein Isabella, Ren Xiaofan, Pfeffer Susanne, Britzen-Laurent Nathalie, Grützmann Robert, Duan Xianglong, Pilarsky Christian
Department of Surgery, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Second Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
Cancers (Basel). 2023 Oct 3;15(19):4842. doi: 10.3390/cancers15194842.
Pancreatic cancer is among the cancers with the highest mortality rates. Most of the patients are found to have advanced cancer, losing the chance of surgical treatment, and there is an urgent need to find new treatment methods. Targeted therapy for specific genes that play a key role in cancer is now an important means to improve the survival rate of patients. We determined that CD73 is highly expressed in pancreatic cancer by flow cytometry and qRT-PCR assays combined with bioinformatics techniques. Application of CRISPR/Cas9 technology to knockout CD73 in human and murine cell lines, respectively, revealed that CD73 inactivation inhibited cell growth and migration and induced G1 cell cycle arrest. We also found that CD73 deletion inhibited the ERK/STAT3 pathway and activated the E-cadherin pathway. In addition, a CRISPR/Cas9 protein kinase library screen was performed and identified Pbk, Fastk, Cdk19, Adck5, Trim28, and Pfkp as possible genes regulating CD73.
胰腺癌是死亡率最高的癌症之一。大多数患者被发现患有晚期癌症，失去了手术治疗的机会，因此迫切需要找到新的治疗方法。针对在癌症中起关键作用的特定基因进行靶向治疗，是目前提高患者生存率的重要手段。我们通过流式细胞术和qRT-PCR检测结合生物信息学技术，确定CD73在胰腺癌中高表达。分别应用CRISPR/Cas9技术在人和小鼠细胞系中敲除CD73，结果显示CD73失活抑制细胞生长和迁移，并诱导G1期细胞周期阻滞。我们还发现，CD73缺失抑制ERK/STAT3通路并激活E-钙黏蛋白通路。此外，进行了CRISPR/Cas9蛋白激酶文库筛选，鉴定出Pbk、Fastk、Cdk19、Adck5、Trim28和Pfkp为可能调控CD73的基因。
