Rab31, a member of the small GTPase family, is crucial in regulating intracellular vesicular transport and signal transduction. It has been associated with various cellular processes such as exosome biogenesis, epithelial-mesenchymal transition (EMT), and endosomal trafficking [1,2,3,4,5,6,7]. Rab31-mediated pathways are involved in diseases like cancer and liver fibrosis [2,3,4,5,7,8]. Genetic models, especially gene-knockout (KO) and conditional-knockout (CKO) mouse models, can be valuable in further exploring its functions.

In gastric cancer, knockdown of Rab31 reduced the number and size of exosomes secreted by cancer cells, and inhibited cell migration in vitro and pulmonary metastasis in vivo, suggesting its role in metastasis through exosome regulation [8]. In cervical cancer, Rab31 knockdown inhibited cell migration, invasion, EMT, and cytoskeletal rearrangement, and promoted the degradation of MAPK6, which was restored by MAPK6 overexpression, indicating its importance in cervical cancer metastasis [3]. In liver fibrosis, knockdown of Rab31 in mouse primary hepatic stellate cells restricted their activation by inhibiting TGF-β receptor II complex endocytosis, and in a mouse CCl4 fibrosis model, it markedly inhibited hepatic fibrosis [5].

In conclusion, Rab31 plays essential roles in multiple biological processes, particularly in diseases such as cancer and liver fibrosis. Findings from KO-like models have revealed its role in processes like exosome-mediated metastasis, cancer cell invasion, and hepatic stellate cell activation, providing insights into potential therapeutic strategies for these diseases.

References:

1. Wei, Denghui, Zhan, Weixiang, Gao, Ying, Gao, Song, Kang, Tiebang. 2020. RAB31 marks and controls an ESCRT-independent exosome pathway. In Cell research, 31, 157-177. doi:10.1038/s41422-020-00409-1. https://pubmed.ncbi.nlm.nih.gov/32958903/

2. Chen, Ke, Xu, Ji, Tong, Yu-Ling, Shen, Xian, Chen, Wei. 2023. Rab31 promotes metastasis and cisplatin resistance in stomach adenocarcinoma through Twist1-mediated EMT. In Cell death & disease, 14, 115. doi:10.1038/s41419-023-05596-4. https://pubmed.ncbi.nlm.nih.gov/36781842/

3. Huang, Yujie, Liu, Ruijuan, Han, Xuechao, Tian, Yonghao, Zhang, Weifang. 2022. Rab31 promotes the invasion and metastasis of cervical cancer cells by inhibiting MAPK6 degradation. In International journal of biological sciences, 18, 112-123. doi:10.7150/ijbs.63388. https://pubmed.ncbi.nlm.nih.gov/34975321/

4. Soelch, Susanne, Beaufort, Nathalie, Loessner, Daniela, Kirchner, Thomas, Magdolen, Viktor. 2021. Rab31-dependent regulation of transforming growth factor ß expression in breast cancer cells. In Molecular medicine (Cambridge, Mass.), 27, 158. doi:10.1186/s10020-021-00419-8. https://pubmed.ncbi.nlm.nih.gov/34906074/

5. Qiu, Chan, Liu, Yi, Huang, Shengjie, He, Song, Zhong, Li. 2022. Rab31 promotes activation of hepatic stellate cells by accelerating TGF-β receptor II complex endocytosis. In The international journal of biochemistry & cell biology, 144, 106170. doi:10.1016/j.biocel.2022.106170. https://pubmed.ncbi.nlm.nih.gov/35091093/

6. Jalagadugula, Gauthami, Mao, Guangfen, Goldfinger, Lawrence E, Poncz, Mortimer, Rao, A Koneti. . Defective RAB31-mediated megakaryocytic early endosomal trafficking of VWF, EGFR, and M6PR in RUNX1 deficiency. In Blood advances, 6, 5100-5112. doi:10.1182/bloodadvances.2021006945. https://pubmed.ncbi.nlm.nih.gov/35839075/

7. Chang, Yu-Chan, Yang, Yi-Fang, Li, Chien-Hsiu, Chen, Chi-Long, Hsiao, Michael. 2024. RAB31 drives extracellular vesicle fusion and cancer-associated fibroblast formation leading to oxaliplatin resistance in colorectal cancer. In Journal of extracellular biology, 3, e141. doi:10.1002/jex2.141. https://pubmed.ncbi.nlm.nih.gov/38939899/

8. Wu, Shan, Tang, Chaotao, Zhang, Qing-Wei, Dong, Zhi-Xia, Wan, Xin-Jian. 2023. Overexpression of RAB31 in gastric cancer is associated with released exosomes and increased tumor cell invasion and metastasis. In Cancer medicine, 12, 13497-13510. doi:10.1002/cam4.6007. https://pubmed.ncbi.nlm.nih.gov/37222416/