Rab25, a member of the Rab GTPase family, shares close homology with Rab11a. It is an epithelial-cell-specific protein governing cell-surface receptors recycling and activation of cellular signaling pathways. This allows it to control a range of cellular functions such as cell proliferation, motility, and death. Endosome recycling regulated by Rab25 is linked to cancer progression, and its study via genetic models can offer insights into its function [1-3].

In mouse models of intestinal and colonic neoplasia, Rab25 deficiency promoted neoplasia development, suggesting it acts as a tumor suppressor in colon carcinogenesis, potentially related to β1-integrin trafficking [1]. In Rab25 -/- male fetal mice, an expanded distal cleft and V-shaped urethral opening were observed, indicating Rab25's role in hypospadias through the β1 integrin/EGFR pathway [2]. Rab25 knockout mice also showed skin barrier dysfunction, increased cell proliferation at the basal layer of the epidermis, and altered expression of epidermal differentiation markers, suggesting its involvement in epidermal differentiation and proliferation regulation [3].

In conclusion, Rab25 plays crucial roles in multiple biological processes. Model-based research, especially KO mouse models, has revealed its significance in cancer, hypospadias, and skin-related conditions. These findings contribute to understanding the underlying mechanisms of these diseases and potentially developing related treatments.

References:

1. Goldenring, J R, Nam, K T. 2010. Rab25 as a tumour suppressor in colon carcinogenesis. In British journal of cancer, 104, 33-6. doi:10.1038/sj.bjc.6605983. https://pubmed.ncbi.nlm.nih.gov/21063400/

2. Zhang, Zhicheng, Zhang, Qiang, Liu, Zhenmin, Wei, Guanghui, Liu, Xing. 2024. Rab25 is involved in hypospadias via the β1 integrin/EGFR pathway. In Experimental cell research, 436, 113980. doi:10.1016/j.yexcr.2024.113980. https://pubmed.ncbi.nlm.nih.gov/38401686/

3. Jeong, Haengdueng, Lim, Kyung-Min, Goldenring, James R, Nam, Ki Taek. . Rab25 Deficiency Perturbs Epidermal Differentiation and Skin Barrier Function in Mice. In Biomolecules & therapeutics, 27, 553-561. doi:10.4062/biomolther.2019.125. https://pubmed.ncbi.nlm.nih.gov/31564077/