Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A genetic interaction between PRUNE and NM23/NDPK has been postulated in Drosophila melanogaster. Many have focused on Drosophila for the genetic combination between PRUNE "knock down" and AWD/NM23 fly mutants bearing the P97S mutation (K-pn, Killer of PRUNE mutation). We postulated a role for PRUNE-NM23 interactions in vertebrate development, demonstrating a physical interaction between the human PRUNE and NM23-H1 proteins, and partially characterizing their functional significance in cancer progression. Here, we present an initial analysis towards the functional characterization of the PRUNE-NM23 interaction during mammalian embryogenesis. Our working hypothesis is that PRUNE, NM23-H1 and their protein-protein interaction partners have important roles in mammalian brain development and adult brain function. Detailed expression analyses from early mouse brain development to adulthood show significant co-expression of these two genes during embryonic stages of brain development, especially focusing on the cortex, hippocampus, midbrain and cerebellum. We hypothesize that their abnormal expression results in an altered pathway of activation, influencing protein complex formation and its protein partner interactions in early embryogenesis. In the adult brain, their function appears concentrated towards their enzyme activities, wherein biochemical variations can result in brain dysfunction.
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PMID:PRUNE and NM23-M1 expression in embryonic and adult mouse brain. 1703 39

The human homolog of the Drosophila prune protein (from PRUNE, which encodes h-prune), which interacts with glycogen synthase kinase 3, promotes cellular motility. H-prune also interacts with nm23-H1, a suppressor of cancer metastasis. It has been reported that stimulation of cellular motility by h-prune is enhanced by its interaction with nm23-H1 in breast cancer cells. In the present study, we examined the expression of h-prune and nm23-H1 during tumor progression in gastric cancer (GC). PRUNE mRNA was overexpressed in 12 (32%) of 38 GC cases by quantitative reverse transcription-polymerase chain reaction. PRUNE mRNA levels correlated significantly with advanced T grade, N grade and tumor stage. Immunohistochemical analysis revealed that 43 (30%) of 143 GC cases were positive for h-prune, and h-prune-positive GC cases showed more advanced T grade, N grade and tumor stage than h-prune-negative GC cases. One hundred and twenty-four (87%) of 143 GC cases were positive for nm23-H1, and nm23-H1 was expressed in almost all (42 cases, 98%) h-prune-positive GC cases. Many GC cases positive for both h-prune and nm23-H1 showed more advanced T grade, N grade and tumor stage than other type GC cases. Patients with h-prune-positive GC had a significantly worse survival rate than patients with h-prune-negative GC. These findings indicate that overexpression of h-prune is associated with tumor progression and aggressiveness of GC. nm23-H1 may enhance motility of cancer cells by interacting with h-prune.
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PMID:Increased expression of h-prune is associated with tumor progression and poor survival in gastric cancer. 1753 57

PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily of molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran and Italy with individuals affected by a new autosomal recessive neurodevelopmental and degenerative disorder in which the cardinal features include primary microcephaly and profound global developmental delay. Our genetic studies identified biallelic mutations of PRUNE1 as responsible. Our functional assays of disease-associated variant alleles revealed impaired microtubule polymerization, as well as cell migration and proliferation properties, of mutant PRUNE. Additionally, our studies also highlight a potential new role for PRUNE during microtubule polymerization, which is essential for the cytoskeletal rearrangements that occur during cellular division and proliferation. Together these studies define PRUNE as a molecule fundamental for normal human cortical development and define cellular and clinical consequences associated with PRUNE mutation.
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PMID:PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment. 2896 77