The important role of stress granules in prostate cancer development, progression, and drug resistance.

1. Gene. 2025 Oct 20;970:149776. doi: 10.1016/j.gene.2025.149776. Epub 2025 Sep 17. The important role of stress granules in prostate cancer development, progression, and drug resistance. Xu Z(1), You H(1), Gu J(2), Jiang J(2), Yan Z(3), Jin X(4). Author information: (1)Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo University, Ningbo, Zhejiang 315010, China; Department of Biochemistry and Molecular Biology, Health Science Center, Ningbo University, Ningbo, Zhejiang 315211, China. (2)Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo University, Ningbo, Zhejiang 315010, China. (3)Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo University, Ningbo, Zhejiang 315010, China. Electronic address: fyyyanzejun@nbu.edu.cn. (4)Department of Biochemistry and Molecular Biology, Health Science Center, Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address: jinxiaofeng@nbu.edu.cn. Prostate cancer (PCa) is the second most prevalent malignancy (7.3 %) and fifth leading cause of cancer death (4.1 %) in men globally. While lung cancer remains the predominant cancer in both incidence and mortality among all cancers, PCa exhibits geographically heterogeneous rising trends. Stress granules (SGs) are membraneless organelles formed through liquid-liquid phase separation (LLPS), playing a pivotal role in cellular stress responses, and are closely associated with various cancers, including PCa. Studies have shown that the expression of key SG-nucleating proteins, such as Ras-GTPase-activating protein-binding protein 1 (G3BP1), is upregulated in PCa, promoting the assembly of SGs. SGs can facilitate the initiation and progression of PCa by regulating mRNA stability, gene expression, and cellular signaling pathways, while also protecting cancer cells from damage under various stress conditions. Furthermore, SGs can modulate androgen receptor (AR) signaling, influencing PCa cell survival and sensitivity to androgen deprivation therapy (ADT). Additionally, SGs can promote PCa resistance to chemotherapy, including docetaxel (DTX), through interactions with various molecules involved in apoptosis, autophagy, and metabolism. This review summarizes the roles of SGs in the development, progression, and drug resistance of PCa, building on current advances in targeting SGs, highlights their promising potential as novel therapeutic targets for inhibiting malignant cancer progression, overcoming therapeutic resistance, and advancing PCa treatment strategies. Copyright © 2025 Elsevier B.V. All rights reserved. DOI: 10.1016/j.gene.2025.149776 PMID: 40972860 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.