International Journal of Clinical Research
International Journal of Clinical Research. 2024; 8: (6) ; 10.12208/j.ijcr.20240198 .
总浏览量: 162
延安大学附属医院妇科 陕西延安
*通讯作者： 雷侠,单位：延安大学附属医院妇科 陕西延安；
宫颈癌和卵巢癌是最常见的妇科恶性肿瘤，其发病率与死亡率近年来有所降低，但是愈加年轻化。囊泡运输是大多数动物细胞调节大分子物质及颗粒性物质穿过细胞膜的一种特殊的转运方式。小GTP酶Rab蛋白是真核生物囊泡运输和膜动力学的主调节因子，介导其转运途径中膜/蛋白质的运输。Rab蛋白是Ras超家族GTP酶的最大分支，在细胞中普遍表达，并且参与调节各种细胞内囊泡运输和不同的细胞内信号通路。Rabs是调节真核生物细胞运输的分子开关。Rab11的活性由鸟嘌呤交换因子和GTP酶激活蛋白控制，它们分别通过调节GTP/GDP交换和内在GTP酶活性来调节其功能。Rab11的过表达已被证明可显着增强囊泡运输。已知Rab11在人类多种癌症中的作用取决于其对内体信号受体分选的控制能力，阻断、干扰和破坏其蛋白调节的基本细胞过程，可以导致肿瘤进展和侵袭。在本综述中，我们讨论了Rab11在细胞内的定位和主要功能及其在妇科两大常见恶性肿瘤进展中的作用。
Cervical cancer and ovarian cancer are the most common gynecological malignant tumors. The incidence and mortality of cervical cancer and ovarian cancer have decreased in recent years, but they are getting younger and younger. Vesicular transport is a special transport mode of macromolecular and granular substances across the cell membrane in most animal cells. Small gtpase Rab proteins are master regulators of vesicle trafficking and membrane dynamics in eukaryotes, mediating membrane/protein trafficking in their transport pathway. Rab proteins, the largest subfamily of Ras gtpases, are ubiquitally expressed in cells and involved in the regulation of various intracellular vesicle trafficking and different intracellular signaling pathways. Rabs are molecular switches that regulate cell trafficking in eukaryotes. Rab11 activity is controlled by guanine exchange factors and gtpase activating proteins, which regulate its function by regulating GTP/GDP exchange and intrinsic gtpase activity, respectively. Overexpression of Rab11 has been shown to significantly enhance vesicular trafficking. The known role of Rab11 in a variety of human cancers depends on its ability to control endosomal signaling receptor sorting, and blocking, interfering, and disrupting fundamental cellular processes regulated by its protein can lead to tumor progression and invasion. In this review, we discuss the intracellular localization and major functions of Rab11 and its role in the progression of two common gynecological malignancies.
[1] Welz T, Wellbourne-Wood J, Kerkhoff E. Orchestration of cell surface proteins by Rab11. Trends Cell Biol. 2014 Jul;24(7):407-15.
[2] Sultana P, Novotny J. Rab11 and Its Role in Neurodegenerative Diseases. ASN Neuro. 2022;14.
[3] Welz T., Wellbourne-Wood J., Kerkhoff E. Orchestration of cell surface proteins by Rab11. Trends Cell Biol. 2014;24:407–415.
[4] Rui-Jian Guo, Yu-Fei Cao, En-Min Li, Li-Yan Xu,Multiple functions and dual characteristics of RAB11A in cancers,Biochimica et Biophysica Acta (BBA) - Reviews on Cancer,Volume 1878, Issue 6,2023,188966,ISSN 0304-419X.
[5] Bai S, Hou W, Yao Y, Meng J, Wei Y, Hu F, Hu X, Wu J, Zhang N, Xu R, Tian F, Wang B, Liao H, Du Y, Fang H, He W, Liu Y, Shen B, Du J. Exocyst controls exosome biogenesis via Rab11a. Mol Ther Nucleic Acids. 2021 Dec 17;27:535-546.
[6] Takahashi, S.; Kubo, K.; Waguri, S.; Yabashi, A.; Shin, H.W.; Katoh, Y.; Nakayama, K. Rab11 regulates exocytosis of recycling vesicles at the plasma membrane. J. Cell Sci.2012, 125, 4049–4057.
[7] Welz T., Wellbourne-Wood J., Kerkhoff E. Orchestration of cell surface proteins by Rab11. Trends Cell Biol. 2014;24:407–415.
[8] Goldenring JR, Shen KR, Vaughan HD, Modlin IM (1993) Identification of a small GTP-binding protein, Rab25, expressed in the gastrointestinal mucosa, kidney, and lung. J Biol Chem 268:18419–18422.
[9] Li G 2011 Rab GTPases, membrane trafficking and diseases. Curr. Drug. Targets 12 1188–1193.
[10] Ali S Z, Langden S, Munkhzul C, et al. Regulatory Mechanism of MicroRNA Expression in Cancer. Int J Mol Sci, 2020,21(5).
[11] 倪琴, 米鑫, 苏雅洁. Rab11蛋白在宫颈癌中的表达及对预后的影响. 中国优生与遗传杂志, 2022, 30 (12): 2150-2153.
[12] Zhang J, Wang F, Xu J, Wang X, Ye F, Xie X. Micro ribonucleic acid-93 promotes oncogenesis of cervical cancer by targeting RAB11 family interacting protein 1. J Obstet Gynaecol Res. 2016 Sep;42(9):1168-79.
[13] Xu H, Yuan Y, Wu W, Zhou M, Jiang Q, Niu L, Ji J, Liu N, Zhang L, Wang X. Hypoxia stimulates invasion and migration of human cervical cancer cell lines HeLa/SiHa through the Rab11 trafficking of integrin αvβ3/FAK/PI3K pathway-mediated Rac1 activation. J Biosci. 2017 Sep;42(3):491-499.
[14] Bhuin T and Roy JK 2015 Rab11 in disease progression.Int. J. Mol. Cell. Med.41–8.
[15] Wang Y, Ren Y, Li N, Zhao J, Zhao S. Rab11a promotes the malignant progression of ovarian cancer by inducing autophagy. Genes Genomics. 2022 Nov;44(11):1375-1384.
[16] Ding J, Wang C, Sun Y, Guo J, Liu S, Cheng Z. Identification of an Autophagy-Related Signature for Prognosis and Immunotherapy Response Prediction in Ovarian Cancer. Biomolecules.2023 Feb 9;13(2):339.
[17] Gao W, Wang X, Zhou Y, Wang X, Yu Y. Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy. Signal Transduct Target Ther. 2022 Jun 20;7(1):196.