FAIM1(Fas apoptotic inhibitory molecule 1)is a highly conserved death receptor antagonist with a total length of 642bp and expresses three different subtypes,FAIM-L,FAIM-M,and FAIM-S.At present,little is known about the function of FAIM1 in cancer and there are no study focused on its roles in non-small cell lung cancer(NSCLC).In our research,we found that FAIM-L was the main subtypes of FAIM1 in NSCLC and was highly expressed in both lung cancer cells and cancer tissues of lung cancer patients.Knocking down FAIM-L significantly inhibited the proliferation and migration of NSCLC cells.Further research showed that absence of FAIM-L exerts tumor suppressive effects not by inducing apoptosis but by inducing autophagy.We found that FAIM-L inhibits autophagy in two ways.first,FAIM-L promoted the formation of mTORC1-ULKl complex,increasing the phosphorylation of Ser757 and inhibiting the activity of ULK1;besides,FAIM-L promots the recruitment of PIK3C3 and BECN1 to 14-3-3?,inhibiting the function of PIK3C3-BECN1 complex.Taken together,our study clarified the function of FAIM-L in NSCLC and discovered the new roles of FAIM-L in autophagy regulation.Thus,this study established a solid theoretical foundation for targeting FAIM-L as a new therapeutic strategy towards NSCLC. |