Mechanotransduction sensing of tissue architecture and cellular microenvironment is a fundamental regulator of cell fate, including
cancer. Meanwhile, long noncoding RNAs (lncRNAs) play multifunctions during
cancer development and treatment. However, the link between lncRNAs and cellular mechanotransduction in the context of
cancer progression has not yet been elucidated. In this study, using atomic force microscopy (AFM), we find that ionizing radiation reduces
tumor stiffness. Ionizing radiation-induced
lncRNA CRYBG3 can blunt YAP/TAZ activity through interference with mechanotransduction, resulting in the inhibition of cell proliferation, invasion, and
metastasis of
lung cancer cells. In vivo, we found that loss of
lncRNA CRYBG3 could power the
tumor initiation and
metastasis ability, but this was abolished by concomitant deplete TAZ. At the molecular level,
lncRNA CRYBG3 that in turn dysregulates
F-actin organization, activates the LATS1/2
kinase, all in all resulting in YAP/TAZ nuclear exclusion. Our research proposes that
lncRNA CRYBG3 is a mediator of
radiotherapy through its control of
cancer-tissue mechanotransduction and wiring YAP/TAZ activity to control
tumor growth and
metastasis.