RAB26: A Potential Therapeutic Target for Advanced Prostate Cancer
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RAB26: A Potential Therapeutic Target for Advanced Prostate Cancer

12/09/2025 Compuscript Ltd

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.
Scopus Cite Score: 8.4 | Impact Factor: 9.4

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Archivos adjuntos
  • (A) Expression density map of single-cell sequencing cell typing in prostate cancer. (B) UMAP diagram of RAB26 in prostate cancer cells. (C) Expression of RAB26 in different cell types. (D) Expression of RAB26 in different tumors. (E) RAB26 and progression-free survival. (F) RAB26 and disease-free survival. (G) The relationship between RAB26 and the T stage of prostate cancer. (H) The relationship between RAB26 and lymph node metastasis in prostate cancer. (I) The relationship between RAB26 and different Gleason scores. (J) Differential expression of RAB26 between normal prostate tissue and prostate cancer tissue. (K) Western blotting detected RAB26 in the tumor and para-carcinoma tissues of patients with prostate cancer. (L) The immunohistochemical staining of RAB26 in patients with prostate cancer. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ∗∗∗∗p < 0.0001.
  • (A) Gross view of mice and tumors. (B) Growth curve of tumor volume. (C) The weight of the tumor. (D) Representative hematoxylin-eosin staining images in the xenograft model of prostate cancer. (E) Western blotting verified the expression of RAB26 in tumor tissue. (F) Representative immunohistochemistry images of epithelial-mesenchymal transition-related markers in tumor tissue. (G) Representative immunohistochemistry images of Bmil, NANOG, and SOX2 in tumor tissue. (H) Imaging of living small animals and gross images of lung metastases. (I) Representative hematoxylin-eosin staining images of a lung metastatic tumor. (J) Representative immunohistochemistry images of MMP2 and MMP9 in lung metastatic tumor. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ∗∗∗∗p < 0.0001.
  • (A, B) The results of GSEA enrichment analysis and representative GSEA data. (C, D) Western blotting and quantitative reverse-transcription PCR detected the expression of epithelial-mesenchymal transition-related marker proteins in PC3, LNCaP, and 22RV1 cells. (E) The relationship between RAB26 and mRNA score. (F) Quantitative reverse-transcription PCR detected the expression of stem cell-related markers in PC3, LNCaP, and 22RV1 cells. (G) RAB26 affected the formation of tumor stem cell spheres in PC3, LNCaP, and 22RV1 cells. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ∗∗∗∗p < 0.0001.
12/09/2025 Compuscript Ltd
Regions: Europe, Ireland, Asia, China
Keywords: Science, Life Sciences

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