ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1616046
This article is part of the Research TopicBiomarker Discovery and Therapeutic Innovations in Genito-Urinary Cancer ManagementView all 11 articles
PCP4 inhibits the progression of prostate cancer through Ca 2+ /CAMKK2/AMPK/AR pathway
Provisionally accepted
- 1Qilu Hospital, Shandong University, Jinan, Shandong Province, China
- 2Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
- 3Shandong University, Jinan, China
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Background: The development of prostate cancer (PCa) remains a major health threat for men worldwide. Calcium/Calmodulin signaling pathway has been implicated to the initiation and progression of diverse human cancers. Loss or downregulation of Purkinje cell protein 4 (PCP4), is frequently observed in some prostate cancer patients, particularly those with castration-resistant prostate cancer (CRPC). Methods: Public datasets were used to analyze PCP4 expression and the relationship between PCP4 expression and clinicopathological characteristics of PCa patients. Gain-and loss-of-function studies in PCa cell lines and mouse models were performed to characterize the role of PCP4 in tumor progression. A series of molecular and biochemical experiments were carried out in PCa cell lines to investigate the mechanism underlying PCP4-mediated tumor suppression. Results: (1) PCP4 gene loss occurs at high frequency in PCa patients, and decreased expression of PCP4 correlates with poor prognosis of PCa, particularly CRPC development; (2) TMPRSS2-ERG fusion frequently co-occurs with PCP4 deletion; (3) PCP4 suppresses prostate cancer progression in vitro and in vivo; (4) PCP4 is an androgen receptor (AR) suppressed gene; (5) PCP4 was involved in the stabilization of CAMKK2 protein; (6) PCP4 inhibits PCa progression by regulating Ca 2+ /CAMKK2/AMPK/AR signaling axis. Conclusion: Our findings elucidate the molecular mechanism that PCP4 downregulation promotes PCa progression via Ca 2+ /CAMKK2/AMPK/AR pathway, highlighting its significance in CRPC development.
Keywords: PCP4, PEP-19, prostate cancer, progression, CRPC Summary：
Received: 22 Apr 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Jia, Yu, Sun, Liu and Han. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bo Han, Shandong University, Jinan, China
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