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

Saravana R.K. Murthy; Evan Dupart; Najla Al-Sweel; Alexander Chen; Niamh X. Cawley; Y. Peng Loh

doi:10.1016/j.canlet.2013.08.011

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

Saravana R.K. Murthy, Evan Dupart, Najla Al-Sweel, Alexander Chen, Niamh X. Cawley, Y. Peng Loh

Division of Hospital Medicine

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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.

Original language	English
Pages (from-to)	204-213
Number of pages	10
Journal	Cancer Letters
Volume	341
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2013.08.011
State	Published - Dec 1 2013

Keywords

Cell invasion
Cell survival
Fibrosarcoma
Hepatocellular carcinoma
Pheochromocytoma

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title = "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.",

keywords = "Cell invasion, Cell survival, Fibrosarcoma, Hepatocellular carcinoma, Pheochromocytoma",

author = "Murthy, {Saravana R.K.} and Evan Dupart and Najla Al-Sweel and Alexander Chen and Cawley, {Niamh X.} and Loh, {Y. Peng}",

note = "Funding Information: This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, USA, ",

year = "2013",

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doi = "10.1016/j.canlet.2013.08.011",

language = "English",

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T1 - Carboxypeptidase E promotes cancer cell survival, but inhibits migration and invasion

AU - Murthy, Saravana R.K.

AU - Dupart, Evan

AU - Al-Sweel, Najla

AU - Chen, Alexander

AU - Cawley, Niamh X.

AU - Loh, Y. Peng

N1 - Funding Information: This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, USA,

PY - 2013/12/1

Y1 - 2013/12/1

N2 - 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.

AB - 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.

KW - Cell invasion

KW - Cell survival

KW - Fibrosarcoma

KW - Hepatocellular carcinoma

KW - Pheochromocytoma

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U2 - 10.1016/j.canlet.2013.08.011

DO - 10.1016/j.canlet.2013.08.011

M3 - Article

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AN - SCOPUS:84887149104

SN - 0304-3835

VL - 341

SP - 204

EP - 213

JO - Cancer Letters

JF - Cancer Letters

IS - 2

ER -

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

Abstract

Keywords

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