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The study aimed to investigate the role of gankyrin in the progression and resistance to androgen deprivation therapy (ADT) of prostate cancer through interactions between tumor cells and tumor-associated macrophages (TAMs). It was found that gankyrin recruits and activates NONO, which increases androgen receptor (AR) expression and leads to the transcription and secretion of HMGB1. HMGB1 recruits and activates TAMs, which secrete IL-6 and further promote prostate cancer progression and ADT resistance through STAT3. Gankyrin expression was found to be a reliable prognostic indicator for prostate cancer, and targeting the interaction between tumor cells and TAMs by blocking this positive feedback loop showed potential for reducing ADT resistance in a tumor xenograft model.
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