| HEF1 is a crucial mediator of the proliferative effects of prostaglandin E(2) on colon cancer cells. | |
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MedLine Citation:
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PMID: 20068165 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Prostaglandin E(2) (PGE(2)), one of the downstream products of cyclooxygenase-2 enzymatic activity, promotes colorectal carcinogenesis in part by stimulating cell division. In this study, we define a critical mechanism in this process by showing that the prometastatic adapter protein human enhancer of filamentation 1 (HEF1; NEDD9) links PGE(2) to the cell cycle machinery in colorectal cancer cells. PGE(2) rapidly induced expression of HEF1 mRNA and protein in colorectal cancer cells. HEF1 overexpression elicited the same effects as PGE(2) treatment on cell proliferation, cell cycle progression, and tumor growth. Conversely, HEF1 knockdown suppressed PGE(2)-driven cell proliferation and cell cycle progression. Cell cycle alterations involved HEF1 fragmentation as well as co-distribution of HEF1 and cell cycle kinase Aurora A along spindle asters during cell division. Moreover, Aurora A co-immunoprecipitated with HEF1 and was activated by HEF1. Consistent with a role for HEF1 in colorectal carcinogenesis, we found elevated expression of HEF1 expression in 50% of human colorectal cancers examined, relative to paired normal tissues. These findings establish that PGE(2) induces HEF1 expression, which in turn promotes cell cycle progression through its interaction with and activation of Aurora A. Further, they establish that HEF1 is a crucial downstream mediator of PGE(2) action during colorectal carcinogenesis. |
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Authors:
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Dianren Xia; Vijaykumar R Holla; Dingzhi Wang; David G Menter; Raymond N DuBois |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-01-12 |
Journal Detail:
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Title: Cancer research Volume: 70 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-15 Completed Date: 2010-03-09 Revised Date: 2011-07-19 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 824-31 Citation Subset: IM |
Affiliation:
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Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
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biosynthesis*,
genetics Animals Cell Cycle / drug effects Cell Growth Processes / drug effects Cell Line, Tumor Colorectal Neoplasms / genetics, metabolism*, pathology* Dinoprostone / pharmacology* Humans Mice Mice, Nude Phosphoproteins / biosynthesis*, genetics Protein-Serine-Threonine Kinases / metabolism RNA, Messenger / biosynthesis, genetics |
| Grant Support | |
ID/Acronym/Agency:
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P01 CA077839-10/CA/NCI NIH HHS; P01 CA77839/CA/NCI NIH HHS; R01 DK062112-09/DK/NIDDK NIH HHS; R25T CA57730/CA/NCI NIH HHS; R37 DK047297-16/DK/NIDDK NIH HHS; R37 DK047297-18/DK/NIDDK NIH HHS; R37 DK47297/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/NEDD9 protein, human; 0/Phosphoproteins; 0/RNA, Messenger; 363-24-6/Dinoprostone; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/aurora kinase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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