Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, P. R. China.
Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China.
Cell Death Dis. 2024 Sep 6;15(9):655. doi: 10.1038/s41419-024-07013-w.
Studies have indicated that RAB17 expression levels are associated with tumor malignancy, and RAB17 is more highly expressed in endometrial cancer (EC) tissues than in peritumoral tissues. However, the roles and potential mechanisms of RAB17 in EC remain undefined. The present study confirmed that the expression of RAB17 facilitates EC progression by suppressing cellular ferroptosis-like alterations. Mechanistically, RAB17 attenuated ferroptosis in EC cells by inhibiting transferrin receptor (TFRC) protein expression in a ubiquitin proteasome-dependent manner. Because EC is a blood-deprived tumor with a poor energy supply, the relationship between RAB17 and hypoglycemia was investigated. RAB17 expression was increased in EC cells incubated in low-glucose medium. Moreover, low-glucose medium limited EC cell ferroptosis and promoted EC progression through the RAB17-TFRC axis. The in vitro results were corroborated by in vivo studies and clinical data. Overall, the present study revealed that increased RAB17 promotes the survival of EC cells during glucose deprivation by inhibiting the onset of TFRC-dependent ferroptosis.
研究表明，RAB17 的表达水平与肿瘤恶性程度相关，并且在子宫内膜癌（EC）组织中的表达水平高于癌旁组织。然而，RAB17 在 EC 中的作用和潜在机制尚不清楚。本研究证实，通过抑制细胞类铁死亡样改变，RAB17 的表达促进了 EC 的进展。在机制上，RAB17 通过泛素蛋白酶体依赖性方式抑制转铁蛋白受体（TFRC）蛋白表达，从而抑制 EC 细胞中的铁死亡。由于 EC 是一种血供不足、能量供应不良的肿瘤，因此研究了 RAB17 与低血糖之间的关系。在低糖培养基中孵育的 EC 细胞中 RAB17 的表达增加。此外，低糖培养基通过 RAB17-TFRC 轴限制 EC 细胞铁死亡并促进 EC 进展。体外研究结果得到了体内研究和临床数据的证实。总的来说，本研究揭示了在葡萄糖剥夺期间，RAB17 通过抑制 TFRC 依赖性铁死亡的发生，促进了 EC 细胞的存活。
