The Cytoplasmic Domain of proEGF Negatively Regulates Motility and Elastinolytic Activity in Thyroid Carcinoma Cells
The intracellular domains of the membrane-anchoring regions of some precursors of epidermal growth factor (EGF) family members have intrinsic biologic activities. We have determined the role of the human proEGF cytoplasmic domain (proEGFcyt) as part of the proEGF transmembrane-anchored region (proEG...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2008-10-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558608801029 |
| _version_ | 1818758786539585536 |
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| author | Aleksandra Glogowska Janette Pyka Astrid Kehlen Marek Los Paul Perumal Ekkehard Weber Sheue-yann Cheng Cuong Hoang-Vu Thomas Klonisch |
| author_facet | Aleksandra Glogowska Janette Pyka Astrid Kehlen Marek Los Paul Perumal Ekkehard Weber Sheue-yann Cheng Cuong Hoang-Vu Thomas Klonisch |
| author_sort | Aleksandra Glogowska |
| collection | DOAJ |
| description | The intracellular domains of the membrane-anchoring regions of some precursors of epidermal growth factor (EGF) family members have intrinsic biologic activities. We have determined the role of the human proEGF cytoplasmic domain (proEGFcyt) as part of the proEGF transmembrane-anchored region (proEGFctF) in the regulation of motility and elastinolytic invasion in human thyroid cancer cells. We found proEGFctF to act as a negative regulator of motility and elastin matrix penetration and the presence of proEGFcyt or proEGF22.23 resulted in a similar reduction in motility and elastinolytic migration. This activity was counteracted by EGF-induced activation of EGF receptor signaling. Decreased elastinolytic migratory activity in the presence of proEGFctF and proEGFcyt/proEGF22.23 coincided with decreased secretion of elastinolytic procathepsin L. The presence of proEGFctF and proEGFcyt/proEGF22.23 coincided with the specific transcriptional up-regulation of t-SNARE member SNAP25. Treatment with siRNA-SNAP25 resulted in motility and elastin migration being restored to normal levels. Epidermal growth factor treatment down-regulated SNAP25 protein by activating EGF receptor-mediated proteasomal degradation of SNAP25. These data provide first evidence for an important function of the cytoplasmic domain of the human proEGF transmembrane region as a novel suppressor of motility and cathepsin L-mediated elastinolytic invasion in human thyroid carcinoma cells and suggest important clinical implications for EGF-expressing tumors. |
| first_indexed | 2024-12-18T06:32:22Z |
| format | Article |
| id | doaj.art-c8387519017a4d728911d762519397de |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-18T06:32:22Z |
| publishDate | 2008-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-c8387519017a4d728911d762519397de2022-12-21T21:17:52ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022008-10-0110101120113010.1593/neo.08580The Cytoplasmic Domain of proEGF Negatively Regulates Motility and Elastinolytic Activity in Thyroid Carcinoma CellsAleksandra Glogowska0Janette Pyka1Astrid Kehlen2Marek Los3Paul Perumal4Ekkehard Weber5Sheue-yann Cheng6Cuong Hoang-Vu7Thomas Klonisch8Department of Human Anatomy and Cell Science, Winnipeg, Manitoba, CanadaClinics of Surgery, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle, GermanyProbiodrug AG, Weinbergweg, Halle, GermanyBioAplications Enterprises, Winnipeg, Manitoba, CanadaDepartment of Human Anatomy and Cell Science, Winnipeg, Manitoba, CanadaInstitute of Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle, GermanyLaboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USAClinics of Surgery, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle, GermanyDepartment of Human Anatomy and Cell Science, Winnipeg, Manitoba, CanadaThe intracellular domains of the membrane-anchoring regions of some precursors of epidermal growth factor (EGF) family members have intrinsic biologic activities. We have determined the role of the human proEGF cytoplasmic domain (proEGFcyt) as part of the proEGF transmembrane-anchored region (proEGFctF) in the regulation of motility and elastinolytic invasion in human thyroid cancer cells. We found proEGFctF to act as a negative regulator of motility and elastin matrix penetration and the presence of proEGFcyt or proEGF22.23 resulted in a similar reduction in motility and elastinolytic migration. This activity was counteracted by EGF-induced activation of EGF receptor signaling. Decreased elastinolytic migratory activity in the presence of proEGFctF and proEGFcyt/proEGF22.23 coincided with decreased secretion of elastinolytic procathepsin L. The presence of proEGFctF and proEGFcyt/proEGF22.23 coincided with the specific transcriptional up-regulation of t-SNARE member SNAP25. Treatment with siRNA-SNAP25 resulted in motility and elastin migration being restored to normal levels. Epidermal growth factor treatment down-regulated SNAP25 protein by activating EGF receptor-mediated proteasomal degradation of SNAP25. These data provide first evidence for an important function of the cytoplasmic domain of the human proEGF transmembrane region as a novel suppressor of motility and cathepsin L-mediated elastinolytic invasion in human thyroid carcinoma cells and suggest important clinical implications for EGF-expressing tumors.http://www.sciencedirect.com/science/article/pii/S1476558608801029 |
| spellingShingle | Aleksandra Glogowska Janette Pyka Astrid Kehlen Marek Los Paul Perumal Ekkehard Weber Sheue-yann Cheng Cuong Hoang-Vu Thomas Klonisch The Cytoplasmic Domain of proEGF Negatively Regulates Motility and Elastinolytic Activity in Thyroid Carcinoma Cells Neoplasia: An International Journal for Oncology Research |
| title | The Cytoplasmic Domain of proEGF Negatively Regulates Motility and Elastinolytic Activity in Thyroid Carcinoma Cells |
| title_full | The Cytoplasmic Domain of proEGF Negatively Regulates Motility and Elastinolytic Activity in Thyroid Carcinoma Cells |
| title_fullStr | The Cytoplasmic Domain of proEGF Negatively Regulates Motility and Elastinolytic Activity in Thyroid Carcinoma Cells |
| title_full_unstemmed | The Cytoplasmic Domain of proEGF Negatively Regulates Motility and Elastinolytic Activity in Thyroid Carcinoma Cells |
| title_short | The Cytoplasmic Domain of proEGF Negatively Regulates Motility and Elastinolytic Activity in Thyroid Carcinoma Cells |
| title_sort | cytoplasmic domain of proegf negatively regulates motility and elastinolytic activity in thyroid carcinoma cells |
| url | http://www.sciencedirect.com/science/article/pii/S1476558608801029 |
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