IndraLab

"Indeed, the co-immunoprecipitation assays showed that wild-type FBXO3 or FBXO3 ΔF , but not FBXO3 ΔApaG , could form stable complexes with USP4 ( xref )."

"Together, these results indicate that FBXO3 binds USP4 to interfere with the interaction between USP4 and DNPEP, leading to stabilization of the USP4 protein."

"Rather, the ApaG domain of FBXO3 is indispensable for FBXO3 interaction with USP4."

"Together, these results indicate that FBXO3 binds USP4 to interfere with the interaction between USP4 and DNPEP, leading to stabilization of the USP4 protein."

"Rather, the ApaG domain of FBXO3 is indispensable for FBXO3 interaction with USP4."

"Mechanistically, we found that the ApaG domain of FBXO3 binds to USP4 to prevent USP4 interaction with DNPEP thereby leading to USP4 protein stabilization."

"FBXO3 can bind to and stabilize USP4, leading to Twist1 protein stabilization and increased breast cancer cell migration and tumor metastasis."

"EMT, an evolutionarily conserved developmental program, has been shown to be related to metastasis via increasing the mobility and invasion of cancer cells, [ xref ] and over 90% of cancer‐related deaths are caused by metastasis. [ xref ] Multiple signaling pathways, such as the TGF signaling pathway, the Notch signaling pathway, and the Wnt/β‐catenin pathway, as well as several transcription factors, including Snail, Zeb, and Twist, have been proved to be involved in the modulation of EMT. [ xref , xref ] Abnormally expressed Twist (also known as Twist1) causes the loss of intercellular adhesion mediated by E‐cadherin, leading to cell metastasis. [ xref , xref ] Studies have reported that Twist1 mediates EMT and metastasis in stomach adenocarcinoma, [ xref ] gliomas, [ xref ] and lung cancer. [ xref ] In addition, Guan et al. reported that the CDK1‐mediated phosphorylation of USP29 promoted the stability of Twist1 and EMT in breast cancer. [ xref ] The E3 ubiquitin ligase FBXO3 can interact with USP4 to stabilize Twist1, thus facilitating breast cancer metastasis. [ xref ] Notably, Twist1‐induced EMT has been implicated in promoting chemoresistance in BC."

"This study reveals a non-canonical function of the E3 ubiquitin ligase FBXO3 in PI3K-induced breast cancer metastasis, showing that FBXO3 binds to and protects USP4 from aspartyl aminopeptidase (DNPEP)-mediated degradation, resulting in Twist1 protein stabilization and increased tumor metastasis."

"FBXO3 can bind to and stabilize USP4, leading to Twist1 protein stabilization and increased breast cancer cell migration and tumor metastasis."

"FBXO3 binds to USP4 and disrupts the interaction between USP4 and DNPEP, leading to stabilization of USP4 and Twist1."

"FBXO3 binds to USP4 and disrupts the interaction between USP4 and DNPEP, leading to stabilization of USP4 and Twist1."