Recent advances in SCF ubiquitin ligase complex: Clinical implications

•F-box proteins play key roles in the development and progression of malignancies.•F-box proteins exert functions mainly via targeting substrates for ubiquitination.•F-box proteins function as oncoproteins or tumor suppressors in different cancers.•F-box proteins inhibitors have been shown to exhibit therapeutic potential.•Targeting F-box proteins could be a strategy for the treatment of human cancers.

F-box proteins, which are subunit recruiting modules of SCF (SKP1-Cullin 1-F-box protein) E3 ligase complexes, play critical roles in the development and progression of human malignancies through governing multiple cellular processes including cell proliferation, apoptosis, invasion and metastasis. Moreover, there are emerging studies that lead to the development of F-box proteins inhibitors with promising therapeutic potential. In this article, we describe how F-box proteins including but not restricted to well-established Fbw7, Skp2 and β-TRCP, are involved in tumorigenesis. However, in-depth investigation is required to further explore the mechanism and the physiological contribution of undetermined F-box proteins in carcinogenesis. Lastly, we suggest that targeting F-box proteins could possibly open new avenues for the treatment and prevention of human cancers.