Abstract
Carboxypeptidase E (CPE), a prohormone processing enzyme is highly expressed and secreted from (neuro)endocrine tumors and gliomas, and has been implicated in cancer progression by promoting tumor growth. Our study demonstrates that secreted or exogenously applied CPE promotes survival of pheochromocytoma (PC12) and hepatocellular carcinoma (MHCC97H) cells under nutrient starvation and hypoxic conditions, but had no effect on their proliferation. CPE also reduced migration and invasion of fibrosarcoma (HT1080) cells. We show that CPE treatment mediates survival of MHCC97H cells during metabolic stress by up-regulating the expression of anti-apoptotic protein BCL-2, and other pro-survival genes, via activation of the ERK1/2 pathway.
Keywords:
Cell invasion; Cell survival; Fibrosarcoma; Hepatocellular carcinoma; Pheochromocytoma.
Published by Elsevier Ireland Ltd.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Carboxypeptidase H / genetics
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Carboxypeptidase H / immunology
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Carboxypeptidase H / metabolism*
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Movement / physiology*
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Cell Proliferation*
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Cell Survival / drug effects
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Cell Survival / physiology
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Immunoblotting
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MAP Kinase Signaling System / drug effects
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Neoplasm Invasiveness
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Neoplasms / genetics
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Neoplasms / metabolism
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Neoplasms / pathology
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PC12 Cells
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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RNA Interference
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Rats
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Recombinant Proteins / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Antibodies, Monoclonal
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Proteins
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Carboxypeptidase H