Protein kinase C modulates negatively the hepatocyte growth factor-induced migration, integrin expression and phosphatidylinositol 3-kinase activation

Gujdár, Annamária; Sipeki, Szabolcs; Bander, Erzsébet; Buday, László; Farago, Anna F.

doi:10.1016/j.cellsig.2003.09.009

Cited by 8 publications

(7 citation statements)

References 40 publications

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“…4, B and C). Consistent with our findings, recent studies have shown that nonselective PKC inhibitors stimulate and PMA attenuates Akt phosphorylation in A549 and HEK293 cells (34) and PKC negatively modulates the hepatocyte growth factor-induced migration, integrin expression, and PI3-K activation in human hepatoma cells (35).…”

Section: Discussionsupporting

confidence: 93%

Signal Transduction Pathways Involved in Oxidative Stress-Induced Intestinal Epithelial Cell Apoptosis

et al. 2005

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Section: Discussionsupporting

confidence: 93%

Signal Transduction Pathways Involved in Oxidative Stress-Induced Intestinal Epithelial Cell Apoptosis

et al. 2005

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“…In accordance with previous studies, we detected significant changes in the expression levels of known Met target genes, including Hmga1, Spp1 (21), Itgβ1 (22), Egr1 (23), and Cldn2 (24). Consecutive functional analysis of the Met target genes allowed a more detailed insight into the cellular machinery associated with the Met-induced phenotype.…”

Section: Figuresupporting

confidence: 90%

Met-regulated expression signature defines a subset of human hepatocellular carcinomas with poor prognosis and aggressive phenotype

Kaposi-Novák

Lee

Gómez–Quiroz

et al. 2006

Journal of Clinical Investigation

352

311

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Identification of specific gene expression signatures characteristic of oncogenic pathways is an important step toward molecular classification of human malignancies. Aberrant activation of the Met signaling pathway is frequently associated with tumor progression and metastasis. In this study, we defined the Met-dependent gene expression signature using global gene expression profiling of WT and Met-deficient primary mouse hepatocytes. Newly identified transcriptional targets of the Met pathway included genes involved in the regulation of oxidative stress responses as well as cell motility, cytoskeletal organization, and angiogenesis. To assess the importance of a Met-regulated gene expression signature, a comparative functional genomic approach was applied to 242 human hepatocellular carcinomas (HCCs) and 7 metastatic liver lesions. Cluster analysis revealed that a subset of human HCCs and all liver metastases shared the Met-induced expression signature. Furthermore, the presence of the Met signature showed significant correlation with increased vascular invasion rate and microvessel density as well as with decreased mean survival time of HCC patients. We conclude that the genetically defined gene expression signatures in combination with comparative functional genomics constitute an attractive paradigm for defining both the function of oncogenic pathways and the clinically relevant subgroups of human cancers.

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“…Although the role of PKC in regulating the migratory activity of tumor cells, such as bladder carcinoma, breast cancer cells, and hepatoma cells, induced by several cytokines has been well established (8,9,(34)(35)(36)(37), which PKC isozymes are responsible for tumor cell migration are not fully explored. Here, we showed that PKC-a was required for migration of hepatoma cell HepG2.…”

Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species Mediated Sustained Activation of Protein Kinase C α and Extracellular Signal-Regulated Kinase for Migration of Human Hepatoma Cell Hepg2

Tsai

Chang

et al. 2006

Molecular Cancer Research

107

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The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) can trigger growth inhibition, epithelial-mesenchymal transition (EMT) -like cell scattering, and migration of hepatoma cells HepG2 in a protein kinase C-A (PKC-A) -dependent manner. Saikosaponin a, an ingredient of antitumorigenic Chinese herb Sho-Saiko-to, inhibited cell growth but did not induce EMT-like cell scattering and cell migration of HepG2. Saikosaponin a and TPA induced transient (for 30 minutes) and sustained (until 6 hours) phosphorylation of extracellular signal-regulated kinase (ERK), respectively. Generation of the reactive oxygen species (ROS) was induced by TPA, but not saikosaponin a, for 3 hours. As expected, scavengers of ROS, such as superoxide dismutase, catalase, and mannitol, and the thiol-containing antioxidant N-acetylcystein dramatically suppressed the TPA-triggered cell migration but not growth inhibition of HepG2. The generation of ROS induced by TPA was PKC, but not ERK, dependent. On the other hand, scavengers of ROS and N-acetylcystein also prevented PKC activation and ERK phosphorylation induced by TPA. On the transcriptional level, TPA can induce gene expression of integrins A 5 , A 6 , and B 1 and reduce gene expression of E-cahedrin in a PKC-and ROS-dependent manner. In conclusion, ROS play a central role in mediating TPA-triggered sustained PKC and ERK signaling for regulation of gene expression of integrins and E-cahedrin that are responsible for EMT and migration of HepG2. (Mol Cancer Res 2006;4(10):747 -58)

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Protein kinase C modulates negatively the hepatocyte growth factor-induced migration, integrin expression and phosphatidylinositol 3-kinase activation

Cited by 8 publications

References 40 publications

Signal Transduction Pathways Involved in Oxidative Stress-Induced Intestinal Epithelial Cell Apoptosis

Signal Transduction Pathways Involved in Oxidative Stress-Induced Intestinal Epithelial Cell Apoptosis

Met-regulated expression signature defines a subset of human hepatocellular carcinomas with poor prognosis and aggressive phenotype

Reactive Oxygen Species Mediated Sustained Activation of Protein Kinase C α and Extracellular Signal-Regulated Kinase for Migration of Human Hepatoma Cell Hepg2

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