PLX298464

GSE137802: IQGAP3 interacts with Rad17 to activate the MRN/ATM/Chk2 signaling and promote radioresistance in lung cancer

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

IQ motif containing GTPase activating protein 3 (IQGAP3) has been implicated in diverse cellular processes including neuronal morphogenesis, cell proliferation and motility as well as epithelial-mesenchymal transition. However, its roles in DNA damage and repair remain to be clarified. Here, we demonstrate that IQGAP3 is frequently overproduced and predicts poor prognosis in lung cancer patients. Functionally, we provide evidence that depletion of IQGAP3 impairs tumorigenesis and overcomes radioresistance in lung cancer in vitro and in vivo. Mechanistically, we uncover that IQGAP3 interacts with and controls the stability of Rad17 to activate the ATM/Chk2 signaling by recruiting Mre11-Rad50-Nbs1 (MRN) complex in response to DNA damage. Moreover, Rad17 is identified as the major downstream effector that mediates the functions of IQGAP3 in lung cancer. Clinically, IQGAP3 overexpression positively correlates with Rad17 protein levels in human lung cancer tissues. Collectively, these data support key roles for IQGAP3 in promoting tumorigenesis and radioresistance in lung cancer by stabilizing the Rad17 protein and suggest targeting IQGAP3 is a promising therapeutic strategy for lung cancer radiotherapy. SOURCE: Qifan Yang (yangqifan@hust.edu.cn) - Huazhong University of Science and Technology