ArticleCancer science2008
Involvement of protein kinase C beta-extracellular signal-regulating kinase 1/2/p38 mitogen-activated protein kinase-heat shock protein 27 activation in hepatocellular carcinoma cell motility and invasion.
Article in Cancer science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Loss of alanine-glyoxylate and serine-pyruvate aminotransferase expression accelerated the progression of hepatocellular carcinoma and predicted poor prognosis.Journal of translational medicine · 2019Pooled it
- Hepatic protein kinase Cβ antagonizing p38American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Resveratrol Impairs Insulin Signaling in Hepatic Cells via Activation of PKC and PTP1B Pathways.International journal of molecular sciences · 2025Article
- Targeting Ser78 phosphorylation of Hsp27 achieves potent antiviral effects against enterovirus A71 infection.Emerging microbes & infections · 2024Article
- Berberine prevents non-alcoholic steatohepatitis-derived hepatocellular carcinoma by inhibiting inflammation and angiogenesis in mice.American journal of translational research · 2019Article
- Hsp27 regulates epithelial mesenchymal transition, metastasis and proliferation in colorectal carcinoma.Oncology letters · 2018Article
- Article
- PKCβ: Expanding role in hepatic adaptation of cholesterol homeostasis to dietary fat/cholesterol.American journal of physiology. Gastrointestinal and liver physiology · 2017Review
- Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance.Molecular and cellular biochemistry · 2017Review
- Molecular mechanism underlying the pharmacological interactions of the protein kinase C-β inhibitor enzastaurin and erlotinib in non-small cell lung cancer cells.American journal of cancer research · 2017Article
- p38α regulates actin cytoskeleton and cytokinesis in hepatocytes during development and aging.PloS one · 2017Article
- The role of HSP27 in RACK1-mediated PKC activation in THP-1 cells.Immunologic research · 2016Article
- A Targetable Molecular Chaperone Hsp27 Confers Aggressiveness in Hepatocellular Carcinoma.Theranostics · 2016Article
- Modulation of Hepatic Protein Kinase Cβ Expression in Metabolic Adaptation to a Lithogenic Diet.Cellular and molecular gastroenterology and hepatology · 2015Article
- Interaction of key pathways in sorafenib-treated hepatocellular carcinoma based on a PCR-array.International journal of clinical and experimental pathology · 2015Article
- Androgen receptor (AR) differential roles in hormone-related tumors including prostate, bladder, kidney, lung, breast and liver.Oncogene · 2014Review
- Emerging role of protein kinase C in energy homeostasis: A brief overview.World journal of diabetes · 2014Review
- Porphyromonas gingivalis promotes invasion of oral squamous cell carcinoma through induction of proMMP9 and its activation.Cellular microbiology · 2014Article
- Prognostic value of peritumoral heat-shock factor-1 in patients receiving resection of hepatocellular carcinoma.British journal of cancer · 2013Article
- Protein kinase C inhibitor AEB071 targets ocular melanoma harboring GNAQ mutations via effects on the PKC/Erk1/2 and PKC/NF-κB pathways.Molecular cancer therapeutics · 2012Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To understand the molecular mechanism that underlies the role of various prominent signal pathways in hepatocellular carcinoma (HCC) metastasis, a human signal transduction oligonucleotide microarray analysis was carried out in cultured HCC cell models with increasing spontaneous metastatic potential (MHCC97L, MHCC97H, and HCCLM6). The results revealed that the mitogen-activated protein kinase (MAPK) pathway is the prominently upregulated pathway in HCC metastasis. Further study showed that basal phosphorylated levels of extracellular signal-regulating kinase (ERK)(1/2) and p38 MAPK consecutively increased from MHCC97L to MHCC97H to HCCLM6 cells, but not c-Jun N-terminal kinase. The phosphorylation of ERK(1/2) and p38 MAPK was regulated by upregulated protein kinase C beta (PKC beta) in HCC cells through the integrated use of PKC beta RNA interference, the PKC beta specific inhibitor enzastaurin and a PKC activator phorbol-12-myristate-13-acetate. Heat shock protein 27 (HSP27) was also verified as a downstream common activated protein of PKC beta-ERK(1/2) and PKC beta-p38 MAPK. In vitro migration and invasion assay further showed that the depletion of PKC beta or inhibition of PKC beta activation effectively decreased HCC cell motility and invasion. Moreover, the motility and invasion of phorbol-12-myristate-13-acetate-stimulated PKC beta-mediated HCC cells was significantly negated by an ERK inhibitor, 1.4-diamino-2.3-dicyano-1.4-bis[2-aminophenylthio] butadiene, or a p38 MAPK inhibitor, 4-(4-Fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole. It also showed that HSP27 is critical in PKC beta-mediated HCC cell motility and invasion. Taken together, this study reveals the important role of this PKC beta-ERK(1/2)/p38MAPK-HSP27 pathway, which was verified for the first time, in modulating HCC cell motility and invasion.
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