E2F1 transactivates IQGAP3 and promotes proliferation of hepatocellular carcinoma cells through IQGAP3-mediated PKC-alpha activation

American Journal of Cancer Research

Min Lin¹  Jieyao Shi²  Yiming Liu³  Qinjian Ke⁴  Xiaokun Ding⁵ 

[1] Central Laboratory, Sanmen Peoples Hospital of Zhejiang, Sanmen, China;Department of Biochemistry and Molecular Biology, School of Medicine, Zhejiang University, Hangzhou, China;Department of General Surgery, Sanmen Peoples Hospital of Zhejiang, Sanmen, China;State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China;Urinary Surgery, Sanmen Peoples Hospital of Zhejiang, Sanmen, China

关键词: E2F1;    IQGAP3;    hepatocellular carcinoma;    PKCα;    activation;    cell proliferation;   

DOI  :  

学科分类：肿瘤学

来源: e-Century Publishing Corporation

【 摘 要 】

For decades, E2F1 has been recognized as a retinoblastoma protein (RB) binding transcription factor that regulates the cell cycle. E2F1 binds preferentially to RB and accelerates the cell cycle in most cancer cells. However, it is thought that E2F1 modulates cell proliferation in other ways as well. Herein, it has been discovered that in pathological tissues derived from hepatocellular carcinoma (HCC) patients, E2F1 correlates positively with IQGAP3 and that both of these factors are highly expressed (N = 164, R = 0.6716). In addition, a high level of E2F1 or IQGAP3 predicted poor survival in HCC patients. Further study determined that E2F1 transactivates IQGAP3, the GTPase binding protein in MHCC-97H cells. Co-immunoprecipitation analysis indicated that IQGAP3 interacts with PKCδ and competitively inhibits the interaction between PKCδ and PKCα, resulting in phosphorylation of PKCα activation and promotion of cell proliferation. This study reveals that highly expressed E2F1 not only transactivates cell-cycle-related factors but also promotes HCC proliferation by activating the phosphorylation of PKCα.

【 授权许可】

CC BY-NC