To address this issue, we analyzed the ZDHHC family of S-acyltransferases to identify critical ZDHHCs involved in LUAD. ZDHHC5 was upregulated at both mRNA and protein levels in LUAD and was associated with an unfavorable prognosis. We found inner centromere protein (INCENP) is the key node connecting the LUAD stem gene network and ZDHHC5 association genes. Protein sequence analysis further predicted Cys15 as the S-palmitoylation site on INCENP protein. As INCENP is a nuclear protein, the nuclear localization of ZDHHC5 protein was predicted in silico and verified by immunofluorescence in the A549 cell line. Our work provides insights into the functions of S-palmitoylation on INCENP and suggests that inhibiting ZDHHC5 is a potential anticancer strategy for CSCs in LUAD.
