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

Abstract

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.