Protein Kinase C-α–Mediated Regulation of Low-Density Lipoprotein Receptor–Related Protein and Urokinase Increases Astrocytoma Invasion

Amos, Samson; Mut, Melike; diPierro, Charles G.; Carpenter, Joan E.; Xiao, Aizhen; Kohutek, Zachary A.; Redpath, Gerard T.; Zhao, Yunge; Wang, Jiahu; Shaffrey, Mark E.; Hussaini, Isa M.

doi:10.1158/0008-5472.can-07-0030

Cited by 40 publications

(31 citation statements)

References 47 publications

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“…We speculate that such a phenomenon was probably due to the impaired invasive ability of aQP4-reduced ln229 cells. similar to migration and adhesion, invasion through the extracellular matrix is an important step in tumor invasion (49). our Matrigel invasion assay demonstrated that reduction of aQP4 led to a decrease in invasiveness of the ln229 cells.…”

Section: Discussionmentioning

confidence: 61%

Role of aquaporin-4 in the regulation of migration and invasion of human glioma cells

Ding

Li³

et al. 2011

Int J Oncol

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Abstract. glioblastoma is the most aggressive form of primary brain tumor with a tendency to invade surrounding healthy brain tissues, rendering tumors of this type largely incurable. aquaporin-4 (aQP4) is a key molecule involved in maintaining water and ion homeostasis in the central nervous system and has been recently reported to play a role in cell migration in addition to its well-known function in brain edema. increased aQP4 expression has been demonstrated in glioblastoma multiforme (gBM), suggesting that it is also involved in malignant brain tumors. Here, we identify a novel role for aquaporin-4 in glioblastoma cell migration and invasion. in the present study, we used small-interference rna technology and a pharmacological inhibitor to knock down the expression of AQP4, which resulted in specific and massive impairment of glioblastoma cell migration and invasion in vitro and in vivo. in addition, we demonstrated the possible mechanisms by which aQP4 functions in the process of glioblastoma cell invasion. the downregulation of matrix metalloprotease-2 (MMP-2) expression in ln229 cells with aQP4 reduction coincided with decreased cell invasive ability. furthermore, our study showed that aQP4 may also be involved in the regulation of glioblastoma cell adhesion. The expression of β-catenin and connexin 43 were increased in aQP4-downregulated ln229 cells consistent with their enhanced cell-cell adhesion ability. in summary, our results indicate that aQP4 is involved in the control of glioblastoma cell migration and invasion and may be a potential therapeutic target for glioblastoma cell infiltration. Introductionglioblastomas are the most common malignant tumors of the adult central nervous system. these are highly invasive and infiltrative tumors which are associated with a poor prognosis and median patient survival of only one year (1,2). a major barrier to available malignant glioma treatment is the invasion of these cells into brain parenchyma. Because of this, local therapies such as surgery or radiation therapy are ineffective (3). glioma cells invade through the ecM of the brain by activating a number of coordinated cellular processes, which include those necessary for migration and invasion. therefore, a detailed understanding of the mechanisms underlying this invasive behavior is essential for the development of novel effective therapies. aQPs (aquaporins) are a family of water channel proteins that provide a major pathway for osmotically driven water transport through cell membranes. to date, 13 aquaporin isoforms (AQP0-AQP12) have been identified in mammalian species (4). Both aQP1 and aQP4 have been clearly identified in brain, and AQP4 is known to participate mainly in brain edema after injury or other brain diseases (5). aQP4 is primarily expressed at the border between brain parenchyma and major fluid compartments, including astrocyte foot processes and glia limitans, as well as ependymal cells and subependymal astrocytes (6). this distribution suggests that aQP4 controls water fluxes into an...

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Section: Discussionmentioning

confidence: 61%

Role of aquaporin-4 in the regulation of migration and invasion of human glioma cells

Ding

Li³

et al. 2011

Int J Oncol

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“…There are many reports proving a close relationship between PKC expression and high invasion and migration of malignant glioma cells [200][201][202][203][204]. As mentioned above, translocation of PKC from the cytosolic fraction to the glioma cell membrane after TPA treatment increases ERK/NF-B-dependent MMP-9 activation and cell migration [200].…”

Section: Gastrointestinal Stromal Tumormentioning

confidence: 89%

“…As mentioned above, translocation of PKC from the cytosolic fraction to the glioma cell membrane after TPA treatment increases ERK/NF-B-dependent MMP-9 activation and cell migration [200]. PKC -induced phosphorylation and downregulation of low-density lipoprotein receptor-related protein stimulate the secretion of uPA and the invasion of glioma cells into the surrounding normal brain tissue [201]. Furthermore, invasion and migration of glioma cells involve several signaling pathways such as PKC -mediated N-cadherin cleavage [202], increased motility by PKC -mediated NG2 phosphorylation at Thr-2256 [203], and PKC or /SRF-mediated RTVP-1 expression [204].…”

Section: Gastrointestinal Stromal Tumormentioning

confidence: 94%

Protein Kinase C (PKC) Isozymes and Cancer

Kang

2014

New Journal of Science

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Protein kinase C (PKC) is a family of phospholipid-dependent serine/threonine kinases, which can be further classified into three PKC isozymes subfamilies: conventional or classic, novel or nonclassic, and atypical. PKC isozymes are known to be involved in cell proliferation, survival, invasion, migration, apoptosis, angiogenesis, and drug resistance. Because of their key roles in cell signaling, PKC isozymes also have the potential to be promising therapeutic targets for several diseases, such as cardiovascular diseases, immune and inflammatory diseases, neurological diseases, metabolic disorders, and multiple types of cancer. This review primarily focuses on the activation, mechanism, and function of PKC isozymes during cancer development and progression.

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“…Therefore the effect of TNF-α appears to be coupled to atypical PKC activation in human dental pulp cells. Currently, the involvement of PKCα in the up-regulation of uPA has been demonstrated [25,26]. Therefore PKCα may be a candidate for the effect of PMA in uPA secretion in human dental pulp cells.…”

Section: Resultsmentioning

confidence: 99%

Protein Kinase C Synergistically Stimulates Tumor Necrosis Factor-α–Induced Secretion of Urokinase-Type Plasminogen Activator in Human Dental Pulp Cells

et al. 2008

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Plasminogen activator (PA) is the enzyme converting plasminogen to its active form, plasmin, involved in various physiological and pathological phenomena. The conversion is catalyzed by two types of PA, urokinase-type PA (uPA) and tissue-type PA (tPA). When human dental pulp cells were stimulated by the inflammatory cytokine tumor necrosis factor-α (TNF-α), PA activity in the conditioned medium was increased, indicating that TNF-α provoked PA secretion. The TNF-α-induced PA release was significantly enhanced in the presence of phorbol-12-myristate-13-acetate (PMA), a protein kinase C (PKC) activator. The PKC inhibitor Ro31-8220 abolished the effect of PMA on the PA release. The activity of PA secreted from the cells stimulated by TNF-α and PMA was reduced by immunoprecipitation using anti-uPA antibody. PMA failed to enhance the TNF-α-induced expression of uPA mRNA. These results suggest that protein kinase C synergistically enhances the secretion of uPA in TNF-α-stimulated human dental pulp cells.

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Protein Kinase C-α–Mediated Regulation of Low-Density Lipoprotein Receptor–Related Protein and Urokinase Increases Astrocytoma Invasion

Cited by 40 publications

References 47 publications

Role of aquaporin-4 in the regulation of migration and invasion of human glioma cells

Role of aquaporin-4 in the regulation of migration and invasion of human glioma cells

Protein Kinase C (PKC) Isozymes and Cancer

Protein Kinase C Synergistically Stimulates Tumor Necrosis Factor-α–Induced Secretion of Urokinase-Type Plasminogen Activator in Human Dental Pulp Cells

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