Sailo Bethsebie Lalduhsaki, Banik Kishore, Girisa Sosmitha, Bordoloi Devivasha, Fan Lu, Halim Clarissa Esmeralda, Wang Hong, Kumar Alan Prem, Zheng Dali, Mao Xinliang, Sethi Gautam, Kunnumakkara Ajaikumar Bahulayan
Cancer Biology Laboratory and DBT-AIST International Laboratory for Advanced Biomedicine (DAILAB), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117 600, Singapore.
Cancers (Basel). 2019 Feb 19;11(2):246. doi: 10.3390/cancers11020246.
The FBXW7 (F-box with 7 tandem WD40) protein encoded by the gene is one of the crucial components of ubiquitin ligase called Skp1-Cullin1-F-box (SCF) complex that aids in the degradation of many oncoproteins via the ubiquitin-proteasome system (UPS) thus regulating cellular growth. FBXW7 is considered as a potent tumor suppressor as most of its target substrates can function as potential growth promoters, including c-Myc, Notch, cyclin E, c-JUN, and KLF5. Its regulators include p53, C/EBP-δ, Numb, microRNAs, Pin 1, Hes-5, BMI1, Ebp2. Mounting evidence has indicated the involvement of aberrant expression of FBXW7 for tumorigenesis. Moreover, numerous studies have also shown its role in cancer cell chemosensitization, thereby demonstrating the importance of FBXW7 in the development of curative cancer therapy. This comprehensive review emphasizes on the targets, functions, regulators and expression of FBXW7 in different cancers and its involvement in sensitizing cancer cells to chemotherapeutic drugs.
由该基因编码的FBXW7（含7个串联WD40的F盒）蛋白是泛素连接酶Skp1-Cullin1-F盒（SCF）复合体的关键组成部分之一，该复合体通过泛素-蛋白酶体系统（UPS）协助降解多种癌蛋白，从而调节细胞生长。FBXW7被认为是一种有效的肿瘤抑制因子，因为其大多数靶底物可作为潜在的生长促进因子发挥作用，包括c-Myc、Notch、细胞周期蛋白E、c-JUN和KLF5。其调节因子包括p53、C/EBP-δ、Numb、微小RNA、Pin 1、Hes-5、BMI1、Ebp2。越来越多的证据表明FBXW7异常表达参与肿瘤发生。此外，大量研究也表明了其在癌细胞化学增敏中的作用，从而证明了FBXW7在癌症治疗性疗法发展中的重要性。这篇综述重点阐述了FBXW7在不同癌症中的靶标、功能、调节因子和表达情况，以及其在使癌细胞对化疗药物敏感化中的作用。
