RESUMEN
Phosphoinositide 3-kinase enhancer (PIKE) belongs to a family of GTP-binding proteins, including three isoforms, PIKE-S, PIKE-L and PIKE-A. PIKE-S and PIKE-L interact with PI3K to enhance the activity of PI3K, but PIKE-A directly binds to AKT and up-regulates its activity. PIKEs also interacts with a variety of signaling molecules in addition to PI3K and AKT, to trigger multiple physiological functions. Overexpression or mutation of PIKE has been observed in a variety of tumors, especially PIKE-A, which acts as a proto-oncogene, promoting cancer cell growth, transformation and invasion through AKT signaling. Knockdown of PIKE-A or blocking of PIKE-A/AKT interactions enhances apoptosis, inhibits cancer cell proliferation, migration and invasion. Moreover, PIKE plays an important role in tumorigenesis through other signaling pathways, such as focal adhesion kinase, signal transducer and activator of transcription 5A, and nuclear factor kappa-light-chain-enhancer of activated B cells. The current review explores the functional role of PIKE and its potential in cancer therapy.
Asunto(s)
Proteínas de Unión al GTP/genética , Proteínas de Unión al GTP/metabolismo , Proteínas Activadoras de GTPasa/genética , Proteínas Activadoras de GTPasa/metabolismo , Neoplasias/metabolismo , Animales , Movimiento Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Terapia Molecular Dirigida , Mutación , Invasividad Neoplásica , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Regulación hacia ArribaRESUMEN
AIM: Ran binding protein M (RanBPM) is a ubiquitous, nucleocytoplasmic protein that serves as a scaffolding molecule. This study aimed to investigate the role of RanBPM in gastric cancer. MATERIALS AND METHODS: RanBPM expression in human gastric cancer tissue samples was analyzed using real-time polymerase chain reaction. The effect of RanBPM on cellular functions was examined in RanBPM-knockdown gastric cells and with in vitro cell functional assays. RESULTS: Gastric tumors with distant metastases expressed lower levels of RanBPM transcripts compared to tumours without detectable metastases (p=0.036). RanBPM knockdown in gastric cancer cells reduced adhesion and promoted survival of gastric cancer cells after exposure to methotrexate and fluorouracil. CONCLUSION: RanBPM levels were reduced in gastric tumors with distant metastases. This suggests that loss of RanBPM expression may play an important role in gastric cancer tumor development and metastasis. Reduced RanBPM expression is also associated with chemoresistance of gastric cancer cells.