New Function Of Flightless-I As An Interaction Protein Of Selective Autophagy Receptor P62

As the frist selective autophagy receptor,p62/SQSTM1 brings ubiquitylated protein aggregates or other cell components into the autophasomes by binding to LC3,and then degrades the ubiquitylated protein aggregates in the autophagy-lysosome.In this paper,we demonstrated a distinctive protein interacting with p62,Flil(flightless-I protein,FliI),which could interfere with the interaction between p62 and LC3,thereby repressing the selective autophagy.On the one hand,Flil inhibited degradation of ubiquitinated protein aggregates through autophagy-lysosomal pathway.On the other hand,FliI promoted accumulation of intracellular oxidized proteins and damaged DNA,and this process relied on p62 presence.Furthermore,in the clinical samples of breast cancer,the expression level of FliI protein in tumor was significantly higher than that in the corresponding para-carcinoma.The expression of FliI protein increased gradually with the progression of breast cancer patients.Accordingly,survival rate of breast cancer patients was negatively correlated with the expression of FliI.These results together indicate that FliI is a cancer-promoting factor in the development of breast cancer.To sum up,our study demonstrates that FliI not only inhibits selective autophagy,but also promotes breast cancer development.This work thus provides a new idea for regulation of selective autophagy and prediction and treatment of breast cancer.