Ji Yuxin, Li Ruonan, Tang Guohui, Wang Wenrui, Chen Changjie, Yang Qingling
Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment, Bengbu Medical University, Bengbu, Anhui, China.
Clinical Testing and Diagnose Experimental Center, Bengbu Medical University, Bengbu, Anhui, China.
Front Oncol. 2025 Mar 24;15:1513360. doi: 10.3389/fonc.2025.1513360. eCollection 2025.
Rab Proteins, A Subfamily Of The Ras Superfamily Of Small Gtpases, Are Critical Regulators Of Intracellular Vesicular Trafficking, Which Is Intricately Linked To Various Cellular Processes. These Proteins Play Essential Roles Not Only In Maintaining Cellular Homeostasis But Also In Mediating The Complex Interplay Between Cancer Cells and Their Microenvironment. Rab Proteins Can Act As Either Oncogenic Factors Or Tumor Suppressors, With Their Functions Highly Dependent On The Cellular Context. Mechanistic Studies Have Revealed That Rab Proteins Are Involved In A Variety Of Processes, Including Vesicular Transport, Tumor Microenvironment Regulation, Autophagy, Drug Resistance, and Metabolic Regulation, and Play Either A Promotional Or Inhibitory Role In Cancer Development. Consequently, Targeting Rab Gtpases To Restore Dysregulated Vesicular Transport Systems May Offer A Promising Therapeutic Strategy To Inhibit Cancer Progression. However, It Is Equally Important To Consider The Potential Risks Of Disrupting Rab Functions, As Their Roles Are Highly Context-Dependent and May Have Opposing Effects In Different Malignancies. This Review Focuses On The Multifaceted Involvement Of Rab Family Proteins In Cancer Progression Underscores Their Importance As Potential Therapeutic Targets and Underscores The Need For A Deeper Understanding Of Their Complex Roles In Tumorigenesis.
Rab蛋白是小GTP酶Ras超家族的一个亚家族,是细胞内囊泡运输的关键调节因子,而细胞内囊泡运输与各种细胞过程有着复杂的联系。这些蛋白不仅在维持细胞稳态方面发挥重要作用,而且在介导癌细胞与其微环境之间的复杂相互作用中也发挥重要作用。Rab蛋白既可以作为致癌因子,也可以作为肿瘤抑制因子,其功能高度依赖于细胞环境。机制研究表明,Rab蛋白参与多种过程,包括囊泡运输、肿瘤微环境调节、自噬、耐药性和代谢调节,并在癌症发展中发挥促进或抑制作用。因此,靶向Rab GTP酶以恢复失调的囊泡运输系统可能为抑制癌症进展提供一种有前景的治疗策略。然而,考虑到破坏Rab功能的潜在风险同样重要,因为它们的作用高度依赖于背景,并且在不同的恶性肿瘤中可能产生相反的效果。本综述重点关注Rab家族蛋白在癌症进展中的多方面参与,强调了它们作为潜在治疗靶点的重要性,并强调了深入了解它们在肿瘤发生中的复杂作用的必要性。