FBXW7 in Cancer: What Has Been Unraveled Thus Far?

• Main Authors: Bethsebie Lalduhsaki Sailo, Kishore Banik, Sosmitha Girisa, Devivasha Bordoloi, Lu Fan, Clarissa Esmeralda Halim, Hong Wang, Alan Prem Kumar, Dali Zheng, Xinliang Mao, Gautam Sethi, Ajaikumar Bahulayan Kunnumakkara
• Format: Article
• Language: English
• Published: MDPI AG 2019-02-01
• Series: Cancers
• Subjects: FBXW7; SCF complex; tumor suppressor; mutations; cancer; chemoresistance; chemosensitization
• Online Access: https://www.mdpi.com/2072-6694/11/2/246
• ISSN: 2072-6694

The FBXW7 (F-box with 7 tandem WD40) protein encoded by the gene <i>FBXW7</i> 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-&#948;, 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.