C1QBP–STAT1 Interaction Promotes Activation of the c-Myc–CHK1/CHK2 Signaling Axis and Radioresistance in Lung Cancer

One of the primary factors contributing to the failure of radiation therapy is the resistance of cancer cells to radiation. The identification of targets of radiation sensitization and exploration of the molecular mechanism of radioresistance are urgently needed. In this study, we demonstrate that the multifunctional chaperone protein C1QBP (component 1Q subcomponent-binding protein) is required for radioresistance and proliferation in lung cancer cells and tissues, C1QBP is significantly overexpressed, indicating poor prognosis. Blocking C1QBP in vivo and in vitro significantly reduces lung cancer proliferation and growth, increasing lung cancer radiosensitivity. In terms of mechanism, we observed that C1QBP interacts with STAT1 and promotes c-Myc-CHK1/CHK2 signaling axis activation. However, STAT1 is necessary for the influence of C1QBP on lung cancer proliferation and radiosensitivity. Implications: These findings establish C1QBP as a key regulator of lung cancer progression and radioresistance, revealing a novel therapeutic avenue for this disease.