Fbxo9, an F-box protein, serves as a substrate receptor for the SKP1-cullin-1-RBX1 ubiquitin ligase. It is involved in multiple biological processes by regulating the ubiquitination and degradation of target proteins, which impacts pathways like cell proliferation, apoptosis, and differentiation [4]. Genetic models, such as gene knockout mouse models, have been crucial in studying its function.

In acute myeloid leukemia (AML), deletion of Fbxo9 in a murine hematopoietic system using a Nuclease technology-based conditional knockout mouse model showed that loss of Fbxo9 led to accelerated and more aggressive leukemia development. Tumors lacking Fbxo9 highly expressed proteins related to metastasis and invasion, and had increased proteasome activity. Tumor cells were also more sensitive to in vitro proteasome inhibition with bortezomib, suggesting Fbxo9 expression may predict patient response to this drug [3].

In hepatocellular carcinoma (HCC), loss-and gain-of-function experiments demonstrated that FBXO9 was overexpressed and facilitated cell proliferation and metastasis both in vitro and in vivo. It is regulated by ZNF143 and targets FBXW7 for ubiquitination and degradation [2].

In lung cancer, knockdown of FBXO9 using lentiviral vectors carrying miRNA-based shRNA sequences promoted metastasis, while overexpression using doxycycline-inducible lentiviral constructs suppressed cell migration, tumor sphere growth, and metastasis by impeding V-ATPase assembly [1].

In summary, Fbxo9 plays diverse and significant roles in various biological processes and disease conditions. The use of knockout and conditional knockout mouse models has been instrumental in uncovering its functions in diseases like AML, HCC, and lung cancer, providing insights into potential therapeutic strategies targeting Fbxo9.