RAB26 identified as a critical regulator of prostate cancer aggressiveness

Prostate cancer (PCa) is one of the most common malignant tumors in men worldwide. While early detection has improved patient outcomes, effective therapies for advanced disease remain limited. Identifying the molecular drivers of PCa growth and metastasis is therefore essential to developing new treatment strategies that can overcome resistance to standard therapies.

In a recent study published in Genes & Diseases, researchers from Chongqing Medical University, revealed the pivotal role of RAB26-a regulator of cell signaling and trafficking-in prostate cancer progression.

Using single-cell RNA sequencing data (GSE141445), researchers found that RAB26 is mainly expressed in luminal and basal/intermediate prostate cancer cells. Elevated RAB26 expression was significantly correlated with advanced pathological stage, higher Gleason score, and poor patient prognosis. Subsequent analyses showed that RAB26 promotes proliferation, migration, and invasion of PCa cells, inhibits apoptosis, and enhances stemness and sphere formation of prostate cancer stem cells (PCSCs).

Transcriptome sequencing analysis indicated that RAB26 drives the metastatic potential of PCa by promoting epithelial–mesenchymal transition through cascades of MAPK/ERK pathways. The team also discovered that RAB26 facilitates the nuclear localization of TWIST1, a key EMT transcription factor, while TWIST1 in turn increases RAB26 expression - creating a positive feedback loop that accelerates cancer progression. Furthermore, the findings were validated in vivo, where RAB26 knockdown significantly reduced tumor size, stemness markers, and lung metastases.

Taken together, these findings identify RAB26 as a critical regulator of prostate cancer aggressiveness. The study underscores its potential both as a prognostic biomarker and as a molecular target for the development of novel therapies aimed at combating advanced and drug-resistant prostate cancer.