Centrosome dysfunction and autophagy dysregulation in renal cell carcinoma: Implications for tumor progression and therapy.

Abstract

Renal cell carcinoma (RCC) is a heterogeneous kidney malignancy driven by complex genetic, molecular, and metabolic alterations. Emerging evidence implicates centrosome dysfunction and autophagy dysregulation in RCC initiation, progression, and resistance to therapy. The centrosome plays a critical role in mitotic fidelity, and its dysfunction often leads to chromosomal and genomic instability. Autophagy, a lysosome-dependent process essential for cellular homeostasis, exhibits a dual role in RCC. It functions as a tumor suppressor in early stages but promotes tumor survival and resistance to therapy in advanced disease. Notably, recent studies indicate that TFEB/TFE3, transcription factors that regulate autophagy and lysosomal biogenesis, mediate a functional interplay between centrosome status and autophagy. This review aims to explore the mechanistic crosstalk between centrosome dysfunction and autophagy in RCC, with a special focus on MiT family translocation RCC, and to discuss emerging therapeutic strategies targeting these pathways.