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Carboxypeptidase E promotes cancer cell survival, but inhibits migration and invasion.

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.
AuthorsSaravana R K Murthy, Evan Dupart, Najla Al-Sweel, Alexander Chen, Niamh X Cawley, Y Peng Loh
JournalCancer letters (Cancer Lett) Vol. 341 Issue 2 Pg. 204-13 (Dec 01 2013) ISSN: 1872-7980 [Electronic] Ireland
PMID23941827 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
CopyrightPublished by Elsevier Ireland Ltd.
Chemical References
  • Antibodies, Monoclonal
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Carboxypeptidase H
Topics
  • Animals
  • Antibodies, Monoclonal (immunology, pharmacology)
  • Carboxypeptidase H (genetics, immunology, metabolism)
  • Cell Line, Tumor
  • Cell Movement (drug effects, physiology)
  • Cell Proliferation
  • Cell Survival (drug effects, physiology)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Humans
  • Immunoblotting
  • MAP Kinase Signaling System (drug effects)
  • Mitogen-Activated Protein Kinase 1 (metabolism)
  • Mitogen-Activated Protein Kinase 3 (metabolism)
  • Neoplasm Invasiveness
  • Neoplasms (genetics, metabolism, pathology)
  • PC12 Cells
  • Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
  • RNA Interference
  • Rats
  • Recombinant Proteins (pharmacology)
  • Reverse Transcriptase Polymerase Chain Reaction

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