Figure 3.

LAT is linked to both hormone-sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC). In untreated HSPC, 5-alpha reductase converts testosterone to dihydrotestosterone (DHT), which binds to the androgen receptor (AR), enters the nucleus, and stimulates LAT3 transcription, resulting in enhanced LAT3 expression and contributes to the mTOR pathway activation. When hormone therapy is used to treat PCa, testosterone levels fall, resulting in castration, and ARs that no longer bind DHT change, increase, and generate splicing variants. AR-V7, in particular, can enter the nucleus in the absence of testosterone activation, and 4F2hc is present in its downstream signaling. Furthermore, the removal of leucine from the cells results in the lack of eIF2 repression and the admission of ATF4 into the nucleus. It enhances LAT1 expression, and LAT1 and 4F2hc form a dimer, allowing leucine into the cell and promoting tumor cell proliferation [54].