A calcium-sensing MCTP1/FYN/MEF2C circuit drives therapy-induced neuroendocrine prostate cancer.

ABSTRACT: Neuroendocrine prostate cancer (NEPC) represents a highly aggressive, treatment‑refractory phenotype that frequently emerges after androgen‑deprivation therapy (ADT). Although perturbed calcium signaling has been implicated in prostate cancer bone metastasis, the specific molecular mechanisms governing NEPC progression remain incompletely characterized. Here, we delineate the MCTP1/FYN/MEF2C signaling axis as a pivotal modulator of intracellular calcium homeostasis that drives neuroendocrine differentiation (NED) and enhances tumor aggressiveness. We demonstrate that ADT upregulates MCTP1, a transmembrane protein with calcium-sensing capabilities, which subsequently activates the Src-family kinase FYN to initiate oncogenic signaling cascades. This activation induces transcriptional upregul

SUBMITTER: Dung PVT 

PROVIDER: S-EPMC12621465 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature