Together, this work demonstrates that FliI functions as a checkpoint protein for selective autophagy in the crosstalk between FliI and p62-recruited cargoes, and its phosphorylation may serve as a prognostic marker for breast cancer.<b>Significance:</b> Flightless-I functions as a checkpoint protein for selective autophagy by interacting with p62 to block its recognition of LC3, leading to tumorigenesis in breast cancer.<i></i>.
Subgroups analysis indicated that katanin P60 positive expression correlated with worse OS in patients of TNM stage II (p= 0.001) and stage III (p=0.001), while no correlation was found between katanin P60 expression and OS in BC patients with stage I (p= 0.538).
However, IL-1 does not significantly elevate the high basal p62 accumulation or high basal autophagy in the ERα<sup>-</sup> /PR<sup>-</sup> BCa cell lines.
Overall, the present study indicated that katanin p60 serves a role in cell proliferation and migration, and thus may be a novel therapeutic target for prevention of breast cancer metastasis.
Further gene expression profiling analysis revealed that p62 was positively correlated with MYC expression level, which mediated the function of p62 in promoting breast cancer stem-like properties.
We conclude that (1) p62 protein is overexpressed in breast cancer; (2) p62 mRNA and protein increase in response to PSI, with no change of basal promoter activity; (3) PDEF upregulates p62 promoter activity through at least two sites; and (4) PSI downregulates PDEF-induced p62 promoter activation through one of these sites.