| 67-kDa laminin receptor increases cGMP to induce cancer-selective apoptosis. | |
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MedLine Citation:
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PMID: 23348740 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The 67-kDa laminin receptor (67LR) is a laminin-binding protein overexpressed in various types of cancer, including bile duct carcinoma, colorectal carcinoma, cervical cancer, and breast carcinoma. 67LR plays a vital role in growth and metastasis of tumor cells and resistance to chemotherapy. Here, we show that 67LR functions as a cancer-specific death receptor. In this cell death receptor pathway, cGMP initiated cancer-specific cell death by activating the PKCδ/acid sphingomyelinase (PKCδ/ASM) pathway. Furthermore, upregulation of cGMP was a rate-determining process of 67LR-dependent cell death induced by the green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG), a natural ligand of 67LR. We found that phosphodiesterase 5 (PDE5), a negative regulator of cGMP, was abnormally expressed in multiple cancers and attenuated 67LR-mediated cell death. Vardenafil, a PDE5 inhibitor that is used to treat erectile dysfunction, significantly potentiated the EGCG-activated 67LR-dependent apoptosis without affecting normal cells and prolonged the survival time in a mouse xenograft model. These results suggest that PDE5 inhibitors could be used to elevate cGMP levels to induce 67LR-mediated, cancer-specific cell death. |
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Authors:
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Motofumi Kumazoe; Kaori Sugihara; Shuntaro Tsukamoto; Yuhui Huang; Yukari Tsurudome; Takashi Suzuki; Yumi Suemasu; Naoki Ueda; Shuya Yamashita; Yoonhee Kim; Koji Yamada; Hirofumi Tachibana |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2013-01-25 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 123 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-04-19 Completed Date: 2013-05-13 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 787-99 Citation Subset: AIM; IM |
Affiliation:
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Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects, physiology* Caspases / metabolism Catechin / analogs & derivatives, pharmacology Cell Line, Tumor Cell Proliferation / drug effects Cyclic GMP / metabolism* Cyclic Nucleotide Phosphodiesterases, Type 5 / metabolism Female Humans Imidazoles / pharmacology Male Membrane Potential, Mitochondrial / drug effects Mice Mice, Inbred BALB C Molecular Weight Multiple Myeloma / drug therapy, metabolism, pathology Neoplasms / drug therapy, metabolism*, pathology* Phosphodiesterase 5 Inhibitors / pharmacology Piperazines / pharmacology Receptors, Laminin / chemistry, metabolism* Signal Transduction Sulfones / pharmacology Triazines / pharmacology Xenograft Model Antitumor Assays |
| Chemical | |
Reg. No./Substance:
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0/Imidazoles; 0/Phosphodiesterase 5 Inhibitors; 0/Piperazines; 0/Receptors, Laminin; 0/Sulfones; 0/Triazines; 154-23-4/Catechin; 7665-99-8/Cyclic GMP; BQM438CTEL/epigallocatechin gallate; EC 3.1.4.35/Cyclic Nucleotide Phosphodiesterases, Type 5; EC 3.4.22.-/Caspases; UCE6F4125H/vardenafil |
| Comments/Corrections | |
Comment In:
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J Clin Invest. 2013 Feb 1;123(2):556-8
[PMID:
23348734
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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