Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As little is known about the role of cadherin-mediated cell-cell adhesion in astrocytes and its alteration in migrating and invasive glioblastomas, we investigated its molecular composition and organisation in primary cultured astrocytes and the T98G and U373MG glioblastoma cell lines. Biochemical and morphological analysis indicated that all three cell types express all of the structural components of the adhesion system, including the LIN-7 PDZ protein, a novel component involved in the organisation of the junctional domain in epithelia and neurons. However, only the astrocytes and T98G cells generated and maintained mature adhesive junctional domains to which LIN-7 was recruited. Alterations in the junctional domain of U373MG cells were associated with higher motility in a poly-L-lysine migration assay. When the T98G cells were cultured on Matrigel matrix, they acquired invasive properties but, despite unchanged cadherin adhesion system protein levels, the invasive T98G cell-cell contacts failed to accumulate LIN-7 and failed to mature. These results identify the LIN-7 PDZ protein as a marker of cell adhesion maturity and cell invasion and indicate that instability and disorganisation of cadherin-mediated junctions rather than reduced expression of cadherin-catenin system components are required to promote migration and invasiveness in glioblastoma cell lines.
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PMID:Invasive behaviour of glioblastoma cell lines is associated with altered organisation of the cadherin-catenin adhesion system. 1214 Feb 64

Glioblastomas are the most aggressive forms of primary brain tumors with their tendency to invade surrounding healthy brain tissues, rendering them largely incurable. In this report, we used small-interference RNA technology to knock down the expression of protein kinase C (PKC) zeta, which resulted in specific and massive impairment of glioblastoma cell migration and invasion. We also explained the fundamental molecular processes of glioblastoma migration and invasion in which PKCzeta is a participant. The silence of PKCzeta expression likewise impaired the phosphorylation of LIN-11, Isl1 and MEC-3 protein domain kinase (LIMK) and cofilin, which is a critical step in cofilin recycling and actin polymerization. Consistent with the defects in cell adhesion, phosphorylation of integrin beta1 was also dampened. Therefore, PKCzeta regulated both cytoskeleton rearrangement and cell adhesion, which contributed to cell migration. Additionally, there was down-regulation of matrix metalloprotease-9 expression in siPKCzeta/LN-229 cells, which coincided with decreased invasion both in vitro and in vivo. These results indicate that PKCzeta is involved in the control of glioblastoma cell migration and invasion by regulating the cytoskeleton rearrangement, cell adhesion, and matrix metalloprotease-9 expression. Collectively, these findings suggest that PKCzeta is a potential therapeutic target for glioblastoma infiltration.
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PMID:Reduction of protein kinase C zeta inhibits migration and invasion of human glioblastoma cells. 1918 46