The CTSZ-TRA2A-IL32 axis defines a targetable macrophage-dependent pathway in metastatic prostate cancer.

ABSTRACT:

Background

Emerging evidence underscores the pivotal role of M2-polarized tumor-associated macrophages (M2-TAMs) in orchestrating immunosuppressive tumor microenvironments that fuel metastatic dissemination in prostate cancer (PCa), yet the fundamental mechanisms governing M2-TAM trafficking in lethal PCa progression remain poorly understood.

Methods

Multi-cohort transcriptomic analyses were performed to identify metastasis-associated genes, with CTSZ prioritized as a key cathepsin linked to prostate cancer progression. Circulating tumor and bone metastatic mouse models were employed to investigate CTSZ-driven M2-TAM infiltration and metastatic behavior. Mechanistic studies included proteasomal degradation assays, IL32 pre-mRNA splicing analysis, and IL-32 binding experiment

SUBMITTER: Chen S 

PROVIDER: S-EPMC12326790 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature