Rab17, a member of the Rab family, is a small GTPase that plays a critical role in the regulation of membrane trafficking in polarized eukaryotic cells [5]. It is involved in processes such as transcytosis, endocytosis, and autophagy, and is known to regulate the intermixing of phagocytosed apoptotic cells with recycling endosomes [3]. Rab17 also mediates the supply of membrane from recycling endosomes to autophagosome-like vacuoles during antibacterial autophagy [6].

In disease-related research, in endometrial cancer (EC), increased RAB17 promotes EC cell survival during glucose deprivation by inhibiting TFRC-dependent ferroptosis [1]. In diabetic foot ulcers (DFUs), the impaired angiogenic capacity may be related to the dysregulated expression of RAB17 in human dermal microvascular endothelial cells, and overexpression of RAB17 enhances angiogenesis and diabetic wound healing [2]. In kidney renal clear cell carcinoma (KIRC), downregulation of RAB17 is correlated with unfavorable clinicopathological characteristics and a worse prognosis, and it may be used as a potential prognostic biomarker [4]. In non-small cell lung cancer (NSCLC), downregulation of Rab17 promotes cell proliferation and invasion through the STAT3/HIF-1α/VEGF signaling pathway [7]. In hepatocellular carcinoma (HCC), Rab17 overexpression inhibits the tumourigenic properties of HCC cells, acting as a tumour suppressor gene, potentially mediated by the Erk pathway [5].

In conclusion, Rab17 is essential for multiple cellular membrane-trafficking processes. Studies using various disease models have revealed its significant roles in cancer development, angiogenesis, and wound healing. Understanding Rab17's functions through these models provides insights into potential therapeutic targets for diseases such as cancer and diabetic complications.

References:

1. Zhou, Xing, Nie, Miaomiao, Xin, Xiaoyan, Yan, Bei, Wang, Hongbo. 2024. RAB17 promotes endometrial cancer progression by inhibiting TFRC-dependent ferroptosis. In Cell death & disease, 15, 655. doi:10.1038/s41419-024-07013-w. https://pubmed.ncbi.nlm.nih.gov/39242574/

2. Du, Hengyu, Li, Shenghong, Lu, Jinqiang, Huang, Yuesheng, Liu, Hongwei. 2023. Single-cell RNA-seq and bulk-seq identify RAB17 as a potential regulator of angiogenesis by human dermal microvascular endothelial cells in diabetic foot ulcers. In Burns & trauma, 11, tkad020. doi:10.1093/burnst/tkad020. https://pubmed.ncbi.nlm.nih.gov/37605780/

3. Yin, Charles, Argintaru, Dean, Heit, Bryan. 2017. Rab17 mediates intermixing of phagocytosed apoptotic cells with recycling endosomes. In Small GTPases, 10, 218-226. doi:10.1080/21541248.2017.1308852. https://pubmed.ncbi.nlm.nih.gov/28471261/

4. Zeng, Zhenhao, Zhang, Zhicheng, Cheng, Xiaofeng, Wang, Xinyi, Wang, Gongxian. 2023. Downregulation of RAB17 have a poor prognosis in kidney renal clear cell carcinoma and its expression correlates with DNA methylation and immune infiltration. In Cellular signalling, 109, 110743. doi:10.1016/j.cellsig.2023.110743. https://pubmed.ncbi.nlm.nih.gov/37269962/

5. Wang, Kejia, Mao, Zhujun, Liu, Li, Yuan, Wenjun, Wei, Li. 2015. Rab17 inhibits the tumourigenic properties of hepatocellular carcinomas via the Erk pathway. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 36, 5815-24. doi:10.1007/s13277-015-3251-3. https://pubmed.ncbi.nlm.nih.gov/25707355/

6. Haobam, Bijaya, Nozawa, Takashi, Minowa-Nozawa, Atsuko, Maruyama, Fumito, Nakagawa, Ichiro. 2014. Rab17-mediated recycling endosomes contribute to autophagosome formation in response to Group A Streptococcus invasion. In Cellular microbiology, 16, 1806-21. doi:10.1111/cmi.12329. https://pubmed.ncbi.nlm.nih.gov/25052408/

7. Wang, Mingliang, Wang, Wendong, Ding, Jingmin, Wang, Jiashun, Zhang, Jun. 2019. Downregulation of Rab17 promotes cell proliferation and invasion in non-small cell lung cancer through STAT3/HIF-1α/VEGF signaling. In Thoracic cancer, 11, 379-388. doi:10.1111/1759-7714.13278. https://pubmed.ncbi.nlm.nih.gov/31841274/