cAMP effects in neuroendocrine tumors: The role of Epac and PKA in cell proliferation and adhesion
cAMP effects have been initially attributed to protein kinase A (PKA) activation. Subsequently, two exchange proteins directly activated by cAMP (Epac1/2) have been identified as cAMP targets. Aim of this study was to investigate cAMP effects in pancreatic-NET (P-NET) and bronchial carcinoids and in...
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| Veröffentlicht in: | Experimental cell research 2015-12, Vol.339 (2), p.241-251 |
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| creator | Vitali, E. Cambiaghi, V. Spada, A. Tresoldi, A. Zerbi, A. Peverelli, E. Carnaghi, C. Mantovani, G. Lania, A.G. |
| description | cAMP effects have been initially attributed to protein kinase A (PKA) activation. Subsequently, two exchange proteins directly activated by cAMP (Epac1/2) have been identified as cAMP targets. Aim of this study was to investigate cAMP effects in pancreatic-NET (P-NET) and bronchial carcinoids and in corresponding cell lines (QGP-1 and H727) on cell proliferation and adhesion and to determine PKA and Epac role in mediating these effects. We found that cAMP increased cyclin D1 expression in P-NET and QGP-1 cells, whereas it had opposite effects on bronchial carcinoids and H727 cells and it promoted cell adhesion in QGP-1 and H727 cells. These effects are mimicked by Epac and PKA specific analogs, activating the small GTPase Rap1.
In conclusion, we demonstrated that cAMP exerted divergent effects on proliferation and promoted cell adhesion of different neuroendocrine cell types, these effects being mediated by both Epac and PKA and involving the same effector GTPase Rap1.
•cAMP increased and decreased cell proliferation in different neuroendocrine cells.•cAMP divergent effects on proliferation are mimicked by both Epac and PKA.•cAMP and its effectors promoted cell adhesion in neuroendocrine tumor cells.•Epac and PKA act through the activation of same effector, Ras-like GTP-ase Rap1. |
| doi_str_mv | 10.1016/j.yexcr.2015.11.011 |
| format | Article |
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In conclusion, we demonstrated that cAMP exerted divergent effects on proliferation and promoted cell adhesion of different neuroendocrine cell types, these effects being mediated by both Epac and PKA and involving the same effector GTPase Rap1.
•cAMP increased and decreased cell proliferation in different neuroendocrine cells.•cAMP divergent effects on proliferation are mimicked by both Epac and PKA.•cAMP and its effectors promoted cell adhesion in neuroendocrine tumor cells.•Epac and PKA act through the activation of same effector, Ras-like GTP-ase Rap1.</description><identifier>ISSN: 0014-4827</identifier><identifier>EISSN: 1090-2422</identifier><identifier>DOI: 10.1016/j.yexcr.2015.11.011</identifier><identifier>PMID: 26589262</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ADHESION ; AMP ; CAMP ; CAMP-dependent Protein Kinase A (PKA) ; Cancer ; Cell Adhesion ; Cell adhesion & migration ; Cell growth ; CELL PROLIFERATION ; Cyclic AMP - metabolism ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Exchange proteins directly activated by cAMP (Epac) ; GTP-ASES ; Guanine Nucleotide Exchange Factors - metabolism ; Humans ; NEOPLASMS ; Neuroendocrine tumors ; Neuroendocrine Tumors - metabolism ; Neuroendocrine Tumors - pathology ; PANCREAS ; PHOSPHOTRANSFERASES ; PROLIFERATION ; Protein expression ; Ras-like GTPase Rap1 ; TUMOR CELLS ; Tumor Cells, Cultured ; Tumorigenesis</subject><ispartof>Experimental cell research, 2015-12, Vol.339 (2), p.241-251</ispartof><rights>2015 Elsevier Inc.</rights><rights>Copyright © 2015 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-13035ca99699cd8f2594bf5e77712857b1c65efcf8109b81d01ca3eb3763076d3</citedby><cites>FETCH-LOGICAL-c415t-13035ca99699cd8f2594bf5e77712857b1c65efcf8109b81d01ca3eb3763076d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014482715301567$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26589262$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22746383$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Vitali, E.</creatorcontrib><creatorcontrib>Cambiaghi, V.</creatorcontrib><creatorcontrib>Spada, A.</creatorcontrib><creatorcontrib>Tresoldi, A.</creatorcontrib><creatorcontrib>Zerbi, A.</creatorcontrib><creatorcontrib>Peverelli, E.</creatorcontrib><creatorcontrib>Carnaghi, C.</creatorcontrib><creatorcontrib>Mantovani, G.</creatorcontrib><creatorcontrib>Lania, A.G.</creatorcontrib><title>cAMP effects in neuroendocrine tumors: The role of Epac and PKA in cell proliferation and adhesion</title><title>Experimental cell research</title><addtitle>Exp Cell Res</addtitle><description>cAMP effects have been initially attributed to protein kinase A (PKA) activation. Subsequently, two exchange proteins directly activated by cAMP (Epac1/2) have been identified as cAMP targets. Aim of this study was to investigate cAMP effects in pancreatic-NET (P-NET) and bronchial carcinoids and in corresponding cell lines (QGP-1 and H727) on cell proliferation and adhesion and to determine PKA and Epac role in mediating these effects. We found that cAMP increased cyclin D1 expression in P-NET and QGP-1 cells, whereas it had opposite effects on bronchial carcinoids and H727 cells and it promoted cell adhesion in QGP-1 and H727 cells. These effects are mimicked by Epac and PKA specific analogs, activating the small GTPase Rap1.
In conclusion, we demonstrated that cAMP exerted divergent effects on proliferation and promoted cell adhesion of different neuroendocrine cell types, these effects being mediated by both Epac and PKA and involving the same effector GTPase Rap1.
•cAMP increased and decreased cell proliferation in different neuroendocrine cells.•cAMP divergent effects on proliferation are mimicked by both Epac and PKA.•cAMP and its effectors promoted cell adhesion in neuroendocrine tumor cells.•Epac and PKA act through the activation of same effector, Ras-like GTP-ase Rap1.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>ADHESION</subject><subject>AMP</subject><subject>CAMP</subject><subject>CAMP-dependent Protein Kinase A (PKA)</subject><subject>Cancer</subject><subject>Cell Adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell growth</subject><subject>CELL PROLIFERATION</subject><subject>Cyclic AMP - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Exchange proteins directly activated by cAMP (Epac)</subject><subject>GTP-ASES</subject><subject>Guanine Nucleotide Exchange Factors - metabolism</subject><subject>Humans</subject><subject>NEOPLASMS</subject><subject>Neuroendocrine tumors</subject><subject>Neuroendocrine Tumors - metabolism</subject><subject>Neuroendocrine Tumors - pathology</subject><subject>PANCREAS</subject><subject>PHOSPHOTRANSFERASES</subject><subject>PROLIFERATION</subject><subject>Protein expression</subject><subject>Ras-like GTPase Rap1</subject><subject>TUMOR CELLS</subject><subject>Tumor Cells, Cultured</subject><subject>Tumorigenesis</subject><issn>0014-4827</issn><issn>1090-2422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFvFCEYhonR2G31F5gYEi9eZuQDhmFMPGyaWo019lDPZIb5yLLZhRVmGvvvZXZrvXkihOd74eEl5A2wGhioD9v6AX_bVHMGTQ1QM4BnZAWsYxWXnD8nK8ZAVlLz9oyc57xljGkN6iU546rRHVd8RQa7_n5L0Tm0U6Y-0IBzihjGaJMPSKd5H1P-SO82SFPcIY2OXh16S_sw0ttv62XE4m5HD-XUO0z95GM4nvbjBnPZvCIvXL_L-PpxvSA_P1_dXX6pbn5cf71c31RWQjNVIJhobN91quvsqB1vOjm4Btu2Ba6bdgCrGnTW6aI4aBgZ2F7gIFolWKtGcUHenXJjnrzJ1k9oNzaGUNQM561UQotCvT9R5cG_ZsyT2fu8GPQB45wNtLJTICTAv8AndBvnFIrDiZJSN7JQ4kTZFHNO6Mwh-X2fHgwwsxRltuZYlFmKMgCGHbPfPmbPwx7Hp5m_zRTg0wnA8mX3HtNihMHi6NMiNEb_3wv-AO3aopE</recordid><startdate>20151210</startdate><enddate>20151210</enddate><creator>Vitali, E.</creator><creator>Cambiaghi, V.</creator><creator>Spada, A.</creator><creator>Tresoldi, A.</creator><creator>Zerbi, A.</creator><creator>Peverelli, E.</creator><creator>Carnaghi, C.</creator><creator>Mantovani, G.</creator><creator>Lania, A.G.</creator><general>Elsevier Inc</general><general>Elsevier BV</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20151210</creationdate><title>cAMP effects in neuroendocrine tumors: The role of Epac and PKA in cell proliferation and adhesion</title><author>Vitali, E. ; Cambiaghi, V. ; Spada, A. ; Tresoldi, A. ; Zerbi, A. ; Peverelli, E. ; Carnaghi, C. ; Mantovani, G. ; Lania, A.G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-13035ca99699cd8f2594bf5e77712857b1c65efcf8109b81d01ca3eb3763076d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>ADHESION</topic><topic>AMP</topic><topic>CAMP</topic><topic>CAMP-dependent Protein Kinase A (PKA)</topic><topic>Cancer</topic><topic>Cell Adhesion</topic><topic>Cell adhesion & migration</topic><topic>Cell growth</topic><topic>CELL PROLIFERATION</topic><topic>Cyclic AMP - metabolism</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Exchange proteins directly activated by cAMP (Epac)</topic><topic>GTP-ASES</topic><topic>Guanine Nucleotide Exchange Factors - metabolism</topic><topic>Humans</topic><topic>NEOPLASMS</topic><topic>Neuroendocrine tumors</topic><topic>Neuroendocrine Tumors - metabolism</topic><topic>Neuroendocrine Tumors - pathology</topic><topic>PANCREAS</topic><topic>PHOSPHOTRANSFERASES</topic><topic>PROLIFERATION</topic><topic>Protein expression</topic><topic>Ras-like GTPase Rap1</topic><topic>TUMOR CELLS</topic><topic>Tumor Cells, Cultured</topic><topic>Tumorigenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vitali, E.</creatorcontrib><creatorcontrib>Cambiaghi, V.</creatorcontrib><creatorcontrib>Spada, A.</creatorcontrib><creatorcontrib>Tresoldi, A.</creatorcontrib><creatorcontrib>Zerbi, A.</creatorcontrib><creatorcontrib>Peverelli, E.</creatorcontrib><creatorcontrib>Carnaghi, C.</creatorcontrib><creatorcontrib>Mantovani, G.</creatorcontrib><creatorcontrib>Lania, A.G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Experimental cell research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vitali, E.</au><au>Cambiaghi, V.</au><au>Spada, A.</au><au>Tresoldi, A.</au><au>Zerbi, A.</au><au>Peverelli, E.</au><au>Carnaghi, C.</au><au>Mantovani, G.</au><au>Lania, A.G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>cAMP effects in neuroendocrine tumors: The role of Epac and PKA in cell proliferation and adhesion</atitle><jtitle>Experimental cell research</jtitle><addtitle>Exp Cell Res</addtitle><date>2015-12-10</date><risdate>2015</risdate><volume>339</volume><issue>2</issue><spage>241</spage><epage>251</epage><pages>241-251</pages><issn>0014-4827</issn><eissn>1090-2422</eissn><abstract>cAMP effects have been initially attributed to protein kinase A (PKA) activation. Subsequently, two exchange proteins directly activated by cAMP (Epac1/2) have been identified as cAMP targets. Aim of this study was to investigate cAMP effects in pancreatic-NET (P-NET) and bronchial carcinoids and in corresponding cell lines (QGP-1 and H727) on cell proliferation and adhesion and to determine PKA and Epac role in mediating these effects. We found that cAMP increased cyclin D1 expression in P-NET and QGP-1 cells, whereas it had opposite effects on bronchial carcinoids and H727 cells and it promoted cell adhesion in QGP-1 and H727 cells. These effects are mimicked by Epac and PKA specific analogs, activating the small GTPase Rap1.
In conclusion, we demonstrated that cAMP exerted divergent effects on proliferation and promoted cell adhesion of different neuroendocrine cell types, these effects being mediated by both Epac and PKA and involving the same effector GTPase Rap1.
•cAMP increased and decreased cell proliferation in different neuroendocrine cells.•cAMP divergent effects on proliferation are mimicked by both Epac and PKA.•cAMP and its effectors promoted cell adhesion in neuroendocrine tumor cells.•Epac and PKA act through the activation of same effector, Ras-like GTP-ase Rap1.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26589262</pmid><doi>10.1016/j.yexcr.2015.11.011</doi><tpages>11</tpages></addata></record> |
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| subjects | 60 APPLIED LIFE SCIENCES ADHESION AMP CAMP CAMP-dependent Protein Kinase A (PKA) Cancer Cell Adhesion Cell adhesion & migration Cell growth CELL PROLIFERATION Cyclic AMP - metabolism Cyclic AMP-Dependent Protein Kinases - metabolism Exchange proteins directly activated by cAMP (Epac) GTP-ASES Guanine Nucleotide Exchange Factors - metabolism Humans NEOPLASMS Neuroendocrine tumors Neuroendocrine Tumors - metabolism Neuroendocrine Tumors - pathology PANCREAS PHOSPHOTRANSFERASES PROLIFERATION Protein expression Ras-like GTPase Rap1 TUMOR CELLS Tumor Cells, Cultured Tumorigenesis |
| title | cAMP effects in neuroendocrine tumors: The role of Epac and PKA in cell proliferation and adhesion |
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