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.
Reference
Title of Original Paper: RAB26 promotes prostate cancer progression via the MAPK/ERK-TWIST1 signaling axis
Journal: Genes & Diseases
Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.
DOI:
https://doi.org/10.1016/j.gendis.2025.101689
Funding Information:
The Chongqing Science and Technology Bureau (China) (No. CSTB2022BSXM-JCX0040).
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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
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