CDK5 activates Hippo signaling to confer resistance to radiotherapy via upregulating TAZ in lung cancer.

Tumor resistance to radiotherapy is a therapeutic challenge in the treatment of patients with lung cancer. Cyclin-dependent kinase 5 (CDK5) has been proposed to participate in cell proliferation, migration and invasion; drug resistance; and immune evasion. However, the functions and regulatory mechanisms of CDK5 in lung cancer radioresistance have not been investigated.We report that CDK5 depletion impairs lung cancer progression and radioresistance in vitro and in vivo. Mechanistically, we identify TAZ, a component of the Hippo pathway, as a key downstream effector of CDK5. CDK5 silencing downregulates TAZ expression and attenuates Hippo signaling activation. Importantly, we provide evidence that TAZ is the major effector mediating the biological functions of CDK5 in lung cancer.These results demonstrate that CDK5 positively modulates the Hippo signaling pathway via TAZ to promote oncogenesis and radioresistance, implying that CDK5 may be a promising radiosensitization target for the treatment of lung cancer.