Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P31749 (AKT)
 22,954 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

F-box protein 11 (FBXO11) has both the E3 ubiquitin ligase activity and the methyltrasferase activity, and regulates metastasis, apoptosis and chemosensitivity in human cancer. However, the clinical significance and biological function of FBXO11 in gastric cancer (GC) are rarely known. Here, we demonstrated up-regulated expression of FBXO11 in GC tissues in comparison with that in tumor-adjacent tissues. Clinical analysis based on our specimens and the TCGA database revealed that FBXO11 overexpression was associated with large tumor size, lymph node metastasis and advanced TNM stage. Notably, GC patients with high FBXO11 expression showed a significant shorter overall survival. Cell proliferation and mobility were measured by CCK-8 and Transwell assays. FBXO11 silencing by transfection with two specific shRNAs attenuated proliferation, migration and invasion of MGC-803 cells. In accordance, FBXO11 overexpression promoted these cellular processes in SGC-7901 cells. Mechanistically, FBXO11 obviously facilitated epithelial-mesenchymal transition (EMT) process as suggested by immunoblotting and immunofluorescence data. Moreover, we found that FBXO11 promoted the activation of AKT pathway with increased phosphorylated AKT level in SGC-7901 cells. LY294002 and Wortmannin, phosphotidylinsitol-3-kinase (PI3K) inhibitors, blocked FBXO11 induced EMT, proliferation, migration and invasion of SGC-7901 cells. Phosphatase and tensin homolog (PTEN), which played a crucial role in regulating PI3K/AKT pathway, was negatively modulated by FBXO11 in GC cells. Taken together, our findings contribute to current understanding of the functions of FBXO11 and suggest a mechanism by which FBXO11 plays an oncogenic role in the development of GC possibly by inhibiting PTEN and subsequently promoting PI3K/AKT pathway activation.
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PMID:F-box protein 11 promotes the growth and metastasis of gastric cancer via PI3K/AKT pathway-mediated EMT. 2927 51