Androgen upregulates the palmitoylation of eIF3L in human prostate LNCaP cells.

Prostate cancer is the second leading cause of cancer-related deaths in Western countries. Most patients diagnosed with advanced prostate cancer can be treated with the main treatment: androgen deprivation therapy (ADT). The androgen receptor (AR) signaling axis plays a pivotal role in the progression of prostate cancer. However, most patients can ultimately progress to the castration-resistant prostate cancer (CRPC) stage within 2 years. At this stage, drugs targeting the AR signaling axis, including enzalutamide and abiraterone acetate, cannot prevent the progression of prostate cancer, thus predicting a poor prognosis. The molecular mechanism lies in the aberrant AR reactivation, which exhibits an adaptive response to ADT, such as the presence of AR splice variants. Thus, CRPC treatment remains a challenge. In addition to the AR axis, a mechanism leading to this progression should be determined. The present study mainly compared palmitoylated proteins between androgen-treated LNCaP cells and non-treated LNCaP cells by palmitoylome profiling, to illustrate the changes at proteomic levels. To screen the androgen-induced palmitoylated proteins, we conducted proteomic experiments using clickable palmitate probe (Alk-C16) between three individual pairs of androgen-treated and non-treated LNCaP cells. We identified 4351 unique peptides corresponding to 835 proteins, among them a number of these identified proteins were palmitoylated proteins, particularly eIF3L. Androgen treatment significantly increased the palmitoylation level of eIF3L, an individual subunit of eIF3. As an initiation factor, eIF3L plays a pivotal role in the translation of mRNAs encoding growth-promoting proteins by enhancing translation rates, thus controlling cell proliferation. In this study, we demonstrated that the regulation of eIF3L palmitoylation may provide new directions for the therapy of prostate cancer. Moreover, the increased level of androgen-induced eIF3L may be used as a biomarker for the diagnosis of early-stage prostate cancer.