and in prostate cancer: from molecular pathways to therapeutic targets: a narrative review.

BACKGROUND AND OBJECTIVE

Prostate cancer is a major cause of cancer-related morbidity and mortality in men globally. The pathogenesis involves complex interactions between genetic mutations and environmental factors, activating multiple signaling pathways, especially Wnt/β-catenin, PI3K/Akt, and NF-κB pathways. Tumor suppressor genes and are key inhibitors of these pathways, crucial in suppressing tumor growth and metastasis. This review synthesizes current knowledge on and in prostate cancer, focusing on their biological functions, regulatory mechanisms, and therapeutic potential.

METHODS

A comprehensive literature review was conducted, examining studies on the molecular biology of and , their expression in prostate cancer, and their impact on processes like proliferation, apoptosis, migration, and invasion.

KEY CONTENT AND FINDINGS

: (I) Inhibition of Wnt/β-catenin signaling: binds to Wnt ligands, preventing receptor interaction and reducing and expression. (II) Promotion of apoptosis: downregulates anti-apoptotic proteins (e.g., ) and upregulates pro-apoptotic proteins (e.g., ), promoting both intrinsic and extrinsic apoptotic pathways. (III) Suppression of epithelial-mesenchymal transition (EMT) and metastasis: inhibits EMT, reduces cell migration, and modulates matrix metalloproteinases (MMPs) to maintain extracellular matrix (ECM) integrity. : (I) Regulation of signaling pathways: modulates Wnt/β-catenin, PI3K/Akt, and NF-κB pathways, reducing cell proliferation. (II) Enhancement of apoptosis: increases activity and upregulates and while reducing apoptosis inhibitors. (III) Inhibition of cell migration and invasion: suppresses EMT, cytoskeletal dynamics proteins like and , and reduces MMPs, limiting invasiveness.

CONCLUSIONS

The tumor suppressor functions of and are critical in the context of prostate cancer. Their ability to inhibit key signaling pathways and promote apoptosis highlights their potential as therapeutic targets. Future research should focus on developing strategies to restore their expression and function, including epigenetic therapies, gene therapy, and small molecule inhibitors. Such approaches could significantly enhance the efficacy of existing treatments and improve patient outcomes.