Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1522282 (EMT)
 2,868 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroblastoma (NB) is the most common malignant tumor in infancy and most common extracranial solid tumor in childhood. With the improvement of diagnosis and treatment, the survival rate of patients with low-risk and intermediate-risk NB can reach up to 90%. In contrast, for high-risk NBs, the long-term survival rate is still <40% because of heterogeneity of this tumor. The pathogenesis of NB is still not explicit, therefore it is of great significance to explore the mechanism of NB tumorigenesis and discover new therapeutic targets for NB. Polo-like kinase 4 (PLK4), one of the polo-like kinase family members, is an important regulator of centriole replication. The aberrant expression of PLK4 was found in several cancers and a recent study has unraveled a novel function of PLK4 as a mediator of invasion and metastasis in Hela and U2OS cells. However, the function of PLK4 in NB development and progression remains to be elucidated. The study showed the expression level of PLK4 in NB tissues was remarkably upregulated and high expression of PLK4 was negatively correlated with clinical features and survival, which suggested that PLK4 could be a potential tumor-promoting factor of NB. Functional studies indicated downregulation of PLK4 suppressed migration and invasion and promoted apoptosis in NB cells. Further experiments showed that downregulation of PLK4 in NB cells inhibited EMT through the PI3K/Akt signaling pathway. Animal experiments demonstrated that the downregulation of PLK4 in SK-N-BE(2) cells dramatically suppressed tumorigenesis and metastasis. PLK4 may be a promising therapeutic target for NB.
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PMID:Polo-like kinase 4 mediates epithelial-mesenchymal transition in neuroblastoma via PI3K/Akt signaling pathway. 2935 13

Neuroblastoma is the most common extracranial solid tumor in children and originates from poorly differentiated neural crest progenitors. High-risk neuroblastoma patients frequently present with metastatic disease at diagnosis. Despite intensive treatment, patients often develop refractory disease characterized by poorly differentiated, therapy resistant cells. Although adjuvant therapy using retinoic acid (RA)-induced differentiation may increase event-free survival, in the majority of cases response to RA-therapy is inadequate. Consequently, current research aims to identify novel therapeutic targets that enhance the sensitivity to RA and induce neuroblastoma cell differentiation. The similarities between neural crest development and neuroblastoma progression provide an appealing starting point. During neural crest development the EMT-transcription factor SNAI2 plays an important role in neural crest specification as well as neural crest cell migration and survival. Here, we report that CRISPR/Cas9 mediated deletion as well as shRNA mediated knockdown of the EMT-transcription factor SNAI2 promotes cellular differentiation in a variety of neuroblastoma models. By comparing mRNA expression data from independent patient cohorts, we show that a SNAI2 activity-based gene expression signature significantly correlates with event-free survival. Loss of SNAI2 function reduces self-renewal, 3D invasion as well as metastatic spread in vivo, while strongly sensitizing neuroblastoma cells to RA-induced growth inhibition. Together, our data demonstrate that SNAI2 maintains progenitor-like features in neuroblastoma cells while interfering with RA-induced growth inhibition. We propose that targeting gene regulatory circuits, such as those controlling SNAI2 function, may allow reversion of RA-therapy resistant neuroblastoma cells to a more differentiated and therapy responsive phenotype.
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PMID:The transcriptional repressor SNAI2 impairs neuroblastoma differentiation and inhibits response to retinoic acid therapy. 3186 4