The topic of palmitoylation in normal stem cells or CSCs is an open issue. To date, the function of palmitoylation has only been reported in neural stem cells, glioma stem cells, and epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance non-small cell lung cancer (NSCLC) cells. Li et al. (2012) found that in normal neural stem cells, ZDHHC5 protein expression declined within minutes following growth factor withdrawal, which led to the induction of neural differentiation in culture. It has been reported that ZDHHC5, ZDHHC17, ZDHHC18, and ZDHHC23 contribute to glioblastoma multiforme development and malignant progression by targeting glioma stem cells (GSC) self-renewal (Chen et al., 2017, 2019, 2020a). The EGFR pathway is closely associated with the stem-like properties in NSCLC (Codony-Servat et al., 2019). Palmitoylation of EGFR enhances its nuclear translocation, and EGFR palmitoylation is important to promote the growth of EGFR-TKI resistance NSCLC cells (Ali et al., 2018). Hence, identifying key ZDHHCs and their stemness substrates is greatly useful for the therapeutic application of LUAD.
