Neurokinin-1 receptor drives PKCɑ-AURKA/N-Myc signaling to facilitate the neuroendocrine progression of prostate cancer.

ABSTRACT: The widespread application of antiandrogen therapies has aroused a significant increase in the incidence of NEPC, a lethal form of the disease lacking efficient clinical treatments. Here we identified a cell surface receptor neurokinin-1 (NK1R) as a clinically relevant driver of treatment-related NEPC (tNEPC). NK1R expression increased in prostate cancer patients, particularly higher in metastatic prostate cancer and treatment-related NEPC, implying a relation with the progression from primary luminal adenocarcinoma toward NEPC. High NK1R level was clinically correlated with accelerated tumor recurrence and poor survival. Mechanical studies identified a regulatory element in the NK1R gene transcription ending region that was recognized by AR. AR inhibition enhanced the expression of NK1R,

SUBMITTER: Zhang XW 

PROVIDER: S-EPMC10310825 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature