LATS2 promotes apoptosis in non-small cell lung cancer A549 cells via triggering Mff-dependent mitochondrial fission and activating the JNK signaling pathway.

LATS2 is a classical tumor suppressor that affects non-small cell lung cancer proliferation and mobilization. However, its role in lung cancer cell apoptosis is unknown. The aim of our study is to explore whether LATS2 activates mitochondria-related apoptosis in lung cancer cells. In the present study, A549 non-small cell lung cancer cells were transfected with a LATS2 adenovirus to induce LATS2 overexpression. Cell apoptosis was evaluated via the MTT assay, TUNEL staining, western blotting, trypan blue staining and ELISA. Mitochondrial function was measured using an immunofluorescence assay, western blotting and ELISA. The results demonstrated that LATS2 was downregulated in A549 lung cancer cells. Overexpression of LATS2 induced A549 cell apoptosis via activating mitochondrial fission. Subsequently, we confirmed that LATS2 modulated mitochondrial fission via the JNK-Mff signaling pathway. Inhibition of the JNK pathway and/or knockdown of Mff abolished the pro-apoptotic effect of LATS2 on A549 cells. Taken together, our results identified LATS2 as a classical tumor suppressor of lung cancer via triggering mitochondrial fission and activating the JNK-Mff signaling pathway. Our results lay the foundation for detailed study of the molecular mechanisms of LATS2 overexpression and regulation of mitochondrial fission for lung cancer treatment.