Fat1 suppresses the tumor-initiating ability of nonsmall cell lung cancer cells by promoting Yes-associated protein 1 nuclear-cytoplasmic translocation

The suppressive roles of Fat1 have been widely revealed in various tumors. However, its effects on the tumor-initiating ability of nonsmall cell lung cancer (NSCLC) cells have never been elucidated. Currently, we identified that a higher level of Fat1 mRNA expression predicted a longer overall survival and first-progression survival of lung cancer patients, especially in adenocarcinoma patients. In addition, Fat1 mRNA exhibited a lower level in lung cancer tissues relative to that in normal tissues. Functionally, we focused on the effects of Fat1 on the tumor-initiating ability of NSCLC cells and we found that Fat1 overexpression decreased the expression of tumor-initiating markers. Furthermore, overexpression of Fat1 reduced ALDH1 activity and sphere-formation ability of NSCLC cells. Mechanistically, we revealed that Fat1 promoted the nuclear-cytoplasmic transportation of YAP1 (Yes-associated protein 1), a critical executor of Hippo signaling, and a mutant form of YAP (YAP-5SA), which can escape from LATS1/2-mediated phosphorylation, rescued the Fat1-mediated inhibition on the tumor-initiating ability of NSCLC cells. This work prompts that Fat1 suppresses the tumor-initiating ability of NSCLC cells by activating Hippo signaling.

Automated summary

Fat1 suppresses the tumor-initiating ability of NSCLC cells by activating Hippo signaling.