Carboxypeptidase E promotes cancer cell survival, but inhibits migration and invasion.
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.
Section on Cellular Neurobiology, Program on Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892. USA.
Saravana R K
SRK
Murthy
Section on Cellular Neurobiology, Program on Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892. USA.
Evan
E
Dupart
Section on Cellular Neurobiology, Program on Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892. USA.
Najla
N
Al-Sweel
Section on Cellular Neurobiology, Program on Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892. USA.
Alexander
A
Chen
Section on Cellular Neurobiology, Program on Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892. USA.
Niamh X
NX
Cawley
Section on Cellular Neurobiology, Program on Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892. USA.
Y Peng
YP
Loh
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D043423:Carboxypeptidase H / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D043423:Carboxypeptidase H
Cell invasion; Cell survival; Fibrosarcoma; Hepatocellular carcinoma; Pheochromocytoma