| Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development. | |
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MedLine Citation:
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PMID: 20141840 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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It is established that tumor cell-derived VEGF acts on endothelial cells to promote angiogenesis and tumor growth. Here, we demonstrate that in K5-SOS-dependent mouse skin tumors, autocrine VEGF is required for tumor cell proliferation in a cell-autonomous and angiogenesis-independent manner. VEGF is upregulated in SOS-expressing tumors, and its deletion in epidermal cells delays tumorigenesis by suppressing angiogenesis and tumor cell proliferation. Epidermis-specific Flt1 deletion also impairs tumorigenesis and proliferation. Surprisingly, complete tumor inhibition occurs in the absence of VEGF in EGFR mutant mice, demonstrating that VEGFR and EGFR synergize in neoplastic cells to promote tumor growth. Mechanistically, K5-SOS upregulates VEGF, Flt1, and Neuropilin-1 in an Erk-dependent manner, thereby activating an autocrine proliferation loop, whereas EGFR prevents tumor cells from apoptosis. Moreover, Flt1 is upregulated in human SCC, and its inhibition in SCC cells impairs proliferation. Thus, in addition to regulating angiogenesis, VEGF has to be considered as a potent growth factor for epidermal tumors. |
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Authors:
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Beate M Lichtenberger; Poi Kiang Tan; Heide Niederleithner; Napoleone Ferrara; Peter Petzelbauer; Maria Sibilia |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell Volume: 140 ISSN: 1097-4172 ISO Abbreviation: Cell Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-02-09 Completed Date: 2010-02-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0413066 Medline TA: Cell Country: United States |
Other Details:
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Languages: eng Pagination: 268-79 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Institute for Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autocrine Communication Carcinoma, Squamous Cell / metabolism* Cell Line, Tumor Cells, Cultured Humans Mice Receptor, Epidermal Growth Factor / genetics, metabolism* Skin Neoplasms / metabolism* Vascular Endothelial Growth Factor A / genetics, metabolism* Vascular Endothelial Growth Factor Receptor-1 / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Vascular Endothelial Growth Factor A; EC 2.7.1.112/Flt1 protein, mouse; EC 2.7.10.1/EGFR protein, mouse; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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