Lysyl oxidase is essential for hypoxia-induced metastasis
Hypoxia in tumours Tumours contain areas of low oxygen (hypoxia) because cancer cells grow and divide so fast that the blood vessels can't keep up with their oxygen requirement. Cells in a hypoxic region are prone to metastasis, but the reasons for this are unknown. Erler et al . have now disco...
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| Veröffentlicht in: | Nature 2006-04, Vol.440 (7088), p.1222-1226 |
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| creator | Erler, Janine T. Bennewith, Kevin L. Nicolau, Monica Dornhöfer, Nadja Kong, Christina Le, Quynh-Thu Chi, Jen-Tsan Ashley Jeffrey, Stefanie S. Giaccia, Amato J. |
| description | Hypoxia in tumours
Tumours contain areas of low oxygen (hypoxia) because cancer cells grow and divide so fast that the blood vessels can't keep up with their oxygen requirement. Cells in a hypoxic region are prone to metastasis, but the reasons for this are unknown. Erler
et al
. have now discovered high levels of the enzyme lysyl oxidase (LOX) in hypoxic cells. High LOX content was associated with a poor prognosis in breast cancer patients. In mice, LOX inhibition reduced metastases, suggesting that it is a possible therapeutic target.
Metastasis is a multistep process responsible for most cancer deaths, and it can be influenced by both the immediate microenvironment (cell–cell or cell–matrix interactions) and the extended tumour microenvironment (for example vascularization)
1
. Hypoxia (low oxygen) is clinically associated with metastasis and poor patient outcome, although the underlying processes remain unclear
2
. Microarray studies have shown the expression of lysyl oxidase (LOX) to be elevated in hypoxic human tumour cells
3
. Paradoxically, LOX expression is associated with both tumour suppression and tumour progression, and its role in tumorigenesis seems dependent on cellular location, cell type and transformation status
4
,
5
,
6
,
7
,
8
,
9
. Here we show that LOX expression is regulated by hypoxia-inducible factor (HIF) and is associated with hypoxia in human breast and head and neck tumours. Patients with high LOX-expressing tumours have poor distant metastasis-free and overall survivals. Inhibition of LOX eliminates metastasis in mice with orthotopically grown breast cancer tumours. Mechanistically, secreted LOX is responsible for the invasive properties of hypoxic human cancer cells through focal adhesion kinase activity and cell to matrix adhesion. Furthermore, LOX may be required to create a niche permissive for metastatic growth. Our findings indicate that LOX is essential for hypoxia-induced metastasis and is a good therapeutic target for preventing and treating metastases. |
| doi_str_mv | 10.1038/nature04695 |
| format | Article |
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Tumours contain areas of low oxygen (hypoxia) because cancer cells grow and divide so fast that the blood vessels can't keep up with their oxygen requirement. Cells in a hypoxic region are prone to metastasis, but the reasons for this are unknown. Erler
et al
. have now discovered high levels of the enzyme lysyl oxidase (LOX) in hypoxic cells. High LOX content was associated with a poor prognosis in breast cancer patients. In mice, LOX inhibition reduced metastases, suggesting that it is a possible therapeutic target.
Metastasis is a multistep process responsible for most cancer deaths, and it can be influenced by both the immediate microenvironment (cell–cell or cell–matrix interactions) and the extended tumour microenvironment (for example vascularization)
1
. Hypoxia (low oxygen) is clinically associated with metastasis and poor patient outcome, although the underlying processes remain unclear
2
. Microarray studies have shown the expression of lysyl oxidase (LOX) to be elevated in hypoxic human tumour cells
3
. Paradoxically, LOX expression is associated with both tumour suppression and tumour progression, and its role in tumorigenesis seems dependent on cellular location, cell type and transformation status
4
,
5
,
6
,
7
,
8
,
9
. Here we show that LOX expression is regulated by hypoxia-inducible factor (HIF) and is associated with hypoxia in human breast and head and neck tumours. Patients with high LOX-expressing tumours have poor distant metastasis-free and overall survivals. Inhibition of LOX eliminates metastasis in mice with orthotopically grown breast cancer tumours. Mechanistically, secreted LOX is responsible for the invasive properties of hypoxic human cancer cells through focal adhesion kinase activity and cell to matrix adhesion. Furthermore, LOX may be required to create a niche permissive for metastatic growth. Our findings indicate that LOX is essential for hypoxia-induced metastasis and is a good therapeutic target for preventing and treating metastases.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/nature04695</identifier><identifier>PMID: 16642001</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adhesion ; Animals ; Biological and medical sciences ; Blood vessels ; Breast cancer ; Cancer ; Cell Hypoxia ; Cell Line, Tumor ; Cell Movement - drug effects ; Clinical outcomes ; Complications and side effects ; Development and progression ; Disease Progression ; Dissemination ; Female ; Focal adhesion kinase ; Gynecology. Andrology. Obstetrics ; Head and neck ; Health aspects ; Humanities and Social Sciences ; Humans ; Hypoxia ; Hypoxia-inducible factors ; Inhibitor drugs ; Invasiveness ; Kinases ; letter ; Liquid oxygen ; Liver Neoplasms - drug therapy ; Liver Neoplasms - pathology ; Liver Neoplasms - secondary ; Lung Neoplasms - drug therapy ; Lung Neoplasms - pathology ; Lung Neoplasms - secondary ; Lysyl oxidase ; Mammary gland diseases ; Medical sciences ; Metastases ; Metastasis ; Mice ; Mice, Nude ; multidisciplinary ; Neoplasm Metastasis - drug therapy ; Neoplasm Metastasis - pathology ; Neoplasm Metastasis - physiopathology ; Neoplasm Transplantation ; Neoplasms - drug therapy ; Neoplasms - enzymology ; Neoplasms - metabolism ; Neoplasms - pathology ; Oncology ; Oxidase ; Oxidases ; Oxygen ; Oxygen requirement ; Physiological aspects ; Protein-Lysine 6-Oxidase - antagonists & inhibitors ; Protein-Lysine 6-Oxidase - metabolism ; Science ; Survival Rate ; Therapeutic applications ; Tumor cell ; Tumor microenvironment ; Tumorigenesis ; Tumors ; Vascularization</subject><ispartof>Nature, 2006-04, Vol.440 (7088), p.1222-1226</ispartof><rights>Springer Nature Limited 2006</rights><rights>2006 INIST-CNRS</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 27, 2006</rights><rights>2006© Nature Publishing Group 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c747t-4d4e0fe379d180f8d55159793d2fbf552a95267ac048a97a5b374f9490c3c0c23</citedby><cites>FETCH-LOGICAL-c747t-4d4e0fe379d180f8d55159793d2fbf552a95267ac048a97a5b374f9490c3c0c23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nature04695$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nature04695$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17735956$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16642001$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Erler, Janine T.</creatorcontrib><creatorcontrib>Bennewith, Kevin L.</creatorcontrib><creatorcontrib>Nicolau, Monica</creatorcontrib><creatorcontrib>Dornhöfer, Nadja</creatorcontrib><creatorcontrib>Kong, Christina</creatorcontrib><creatorcontrib>Le, Quynh-Thu</creatorcontrib><creatorcontrib>Chi, Jen-Tsan Ashley</creatorcontrib><creatorcontrib>Jeffrey, Stefanie S.</creatorcontrib><creatorcontrib>Giaccia, Amato J.</creatorcontrib><title>Lysyl oxidase is essential for hypoxia-induced metastasis</title><title>Nature</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>Hypoxia in tumours
Tumours contain areas of low oxygen (hypoxia) because cancer cells grow and divide so fast that the blood vessels can't keep up with their oxygen requirement. Cells in a hypoxic region are prone to metastasis, but the reasons for this are unknown. Erler
et al
. have now discovered high levels of the enzyme lysyl oxidase (LOX) in hypoxic cells. High LOX content was associated with a poor prognosis in breast cancer patients. In mice, LOX inhibition reduced metastases, suggesting that it is a possible therapeutic target.
Metastasis is a multistep process responsible for most cancer deaths, and it can be influenced by both the immediate microenvironment (cell–cell or cell–matrix interactions) and the extended tumour microenvironment (for example vascularization)
1
. Hypoxia (low oxygen) is clinically associated with metastasis and poor patient outcome, although the underlying processes remain unclear
2
. Microarray studies have shown the expression of lysyl oxidase (LOX) to be elevated in hypoxic human tumour cells
3
. Paradoxically, LOX expression is associated with both tumour suppression and tumour progression, and its role in tumorigenesis seems dependent on cellular location, cell type and transformation status
4
,
5
,
6
,
7
,
8
,
9
. Here we show that LOX expression is regulated by hypoxia-inducible factor (HIF) and is associated with hypoxia in human breast and head and neck tumours. Patients with high LOX-expressing tumours have poor distant metastasis-free and overall survivals. Inhibition of LOX eliminates metastasis in mice with orthotopically grown breast cancer tumours. Mechanistically, secreted LOX is responsible for the invasive properties of hypoxic human cancer cells through focal adhesion kinase activity and cell to matrix adhesion. Furthermore, LOX may be required to create a niche permissive for metastatic growth. Our findings indicate that LOX is essential for hypoxia-induced metastasis and is a good therapeutic target for preventing and treating metastases.</description><subject>Adhesion</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood vessels</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cell Hypoxia</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Clinical outcomes</subject><subject>Complications and side effects</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>Dissemination</subject><subject>Female</subject><subject>Focal adhesion kinase</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Head and neck</subject><subject>Health aspects</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Hypoxia-inducible factors</subject><subject>Inhibitor drugs</subject><subject>Invasiveness</subject><subject>Kinases</subject><subject>letter</subject><subject>Liquid oxygen</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - secondary</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - secondary</subject><subject>Lysyl oxidase</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>multidisciplinary</subject><subject>Neoplasm Metastasis - drug therapy</subject><subject>Neoplasm Metastasis - pathology</subject><subject>Neoplasm Metastasis - physiopathology</subject><subject>Neoplasm Transplantation</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - enzymology</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Oncology</subject><subject>Oxidase</subject><subject>Oxidases</subject><subject>Oxygen</subject><subject>Oxygen requirement</subject><subject>Physiological aspects</subject><subject>Protein-Lysine 6-Oxidase - antagonists & inhibitors</subject><subject>Protein-Lysine 6-Oxidase - metabolism</subject><subject>Science</subject><subject>Survival Rate</subject><subject>Therapeutic applications</subject><subject>Tumor cell</subject><subject>Tumor microenvironment</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Vascularization</subject><issn>0028-0836</issn><issn>1476-4687</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN09tr2zAUB2AxNtas29Peh1nZYGzudJf1WMouhcBgl2ehyEeZiiOnkg3Nfz-VBOKMlBYbDNKnn459LIReE3xOMGs-RzuMCTCXWjxBM8KVrLls1FM0w5g2NW6YPEEvcr7GGAui-HN0QqTkFGMyQ3q-yZuu6m9DazNUIVeQM8Qh2K7yfar-btZlztYhtqODtlrBYHO5Q36JnnnbZXi1e56iP1-__L78Xs9_fLu6vJjXTnE11LzlgD0wpVvSYN-0QhChlWYt9QsvBLVaUKmsw7yxWlmxYIp7zTV2zGFH2Sl6v81dp_5mhDyYVcgOus5G6MdsmKCCNuxhSBRhShFV4Nl_8LofUywvYWipU3CitCzq7b0Kc1G-H9cF1Vu0tB2YEH0_JOuWECHZro_gQxm-kBJTxYhkj_SkEVxQQtW-iAPv1uHGTEPvRdOk8yOoXC2sgjta6qMWTHf4cLCgmAFuh6UdczZXv34ehj9kp7kft9alPucE3qxTWNm0MQSbuxNgJieg6De7to2LFbR7u_vlC3i3AzY72_lkowt575RiQou7_n_aulym4hLSvv_H9v0HvMIVRQ</recordid><startdate>20060427</startdate><enddate>20060427</enddate><creator>Erler, 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oxidase is essential for hypoxia-induced metastasis</title><author>Erler, Janine T. ; Bennewith, Kevin L. ; Nicolau, Monica ; Dornhöfer, Nadja ; Kong, Christina ; Le, Quynh-Thu ; Chi, Jen-Tsan Ashley ; Jeffrey, Stefanie S. ; Giaccia, Amato J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c747t-4d4e0fe379d180f8d55159793d2fbf552a95267ac048a97a5b374f9490c3c0c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adhesion</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood vessels</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cell Hypoxia</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Clinical outcomes</topic><topic>Complications and side effects</topic><topic>Development and progression</topic><topic>Disease Progression</topic><topic>Dissemination</topic><topic>Female</topic><topic>Focal adhesion kinase</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Head and neck</topic><topic>Health aspects</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Hypoxia-inducible factors</topic><topic>Inhibitor drugs</topic><topic>Invasiveness</topic><topic>Kinases</topic><topic>letter</topic><topic>Liquid oxygen</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver Neoplasms - secondary</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - secondary</topic><topic>Lysyl oxidase</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>multidisciplinary</topic><topic>Neoplasm Metastasis - drug therapy</topic><topic>Neoplasm Metastasis - pathology</topic><topic>Neoplasm Metastasis - physiopathology</topic><topic>Neoplasm Transplantation</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - enzymology</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - pathology</topic><topic>Oncology</topic><topic>Oxidase</topic><topic>Oxidases</topic><topic>Oxygen</topic><topic>Oxygen requirement</topic><topic>Physiological aspects</topic><topic>Protein-Lysine 6-Oxidase - antagonists & inhibitors</topic><topic>Protein-Lysine 6-Oxidase - metabolism</topic><topic>Science</topic><topic>Survival Rate</topic><topic>Therapeutic applications</topic><topic>Tumor cell</topic><topic>Tumor microenvironment</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><topic>Vascularization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Erler, Janine T.</creatorcontrib><creatorcontrib>Bennewith, Kevin L.</creatorcontrib><creatorcontrib>Nicolau, Monica</creatorcontrib><creatorcontrib>Dornhöfer, Nadja</creatorcontrib><creatorcontrib>Kong, Christina</creatorcontrib><creatorcontrib>Le, Quynh-Thu</creatorcontrib><creatorcontrib>Chi, Jen-Tsan Ashley</creatorcontrib><creatorcontrib>Jeffrey, Stefanie S.</creatorcontrib><creatorcontrib>Giaccia, Amato J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>University of Michigan</collection><collection>Genetics Abstracts</collection><collection>SIRS Editorial</collection><collection>Environment Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><jtitle>Nature</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Erler, Janine T.</au><au>Bennewith, Kevin L.</au><au>Nicolau, Monica</au><au>Dornhöfer, Nadja</au><au>Kong, Christina</au><au>Le, Quynh-Thu</au><au>Chi, Jen-Tsan Ashley</au><au>Jeffrey, Stefanie S.</au><au>Giaccia, Amato J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lysyl oxidase is essential for hypoxia-induced metastasis</atitle><jtitle>Nature</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2006-04-27</date><risdate>2006</risdate><volume>440</volume><issue>7088</issue><spage>1222</spage><epage>1226</epage><pages>1222-1226</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><eissn>1476-4679</eissn><coden>NATUAS</coden><abstract>Hypoxia in tumours
Tumours contain areas of low oxygen (hypoxia) because cancer cells grow and divide so fast that the blood vessels can't keep up with their oxygen requirement. Cells in a hypoxic region are prone to metastasis, but the reasons for this are unknown. Erler
et al
. have now discovered high levels of the enzyme lysyl oxidase (LOX) in hypoxic cells. High LOX content was associated with a poor prognosis in breast cancer patients. In mice, LOX inhibition reduced metastases, suggesting that it is a possible therapeutic target.
Metastasis is a multistep process responsible for most cancer deaths, and it can be influenced by both the immediate microenvironment (cell–cell or cell–matrix interactions) and the extended tumour microenvironment (for example vascularization)
1
. Hypoxia (low oxygen) is clinically associated with metastasis and poor patient outcome, although the underlying processes remain unclear
2
. Microarray studies have shown the expression of lysyl oxidase (LOX) to be elevated in hypoxic human tumour cells
3
. Paradoxically, LOX expression is associated with both tumour suppression and tumour progression, and its role in tumorigenesis seems dependent on cellular location, cell type and transformation status
4
,
5
,
6
,
7
,
8
,
9
. Here we show that LOX expression is regulated by hypoxia-inducible factor (HIF) and is associated with hypoxia in human breast and head and neck tumours. Patients with high LOX-expressing tumours have poor distant metastasis-free and overall survivals. Inhibition of LOX eliminates metastasis in mice with orthotopically grown breast cancer tumours. Mechanistically, secreted LOX is responsible for the invasive properties of hypoxic human cancer cells through focal adhesion kinase activity and cell to matrix adhesion. Furthermore, LOX may be required to create a niche permissive for metastatic growth. Our findings indicate that LOX is essential for hypoxia-induced metastasis and is a good therapeutic target for preventing and treating metastases.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16642001</pmid><doi>10.1038/nature04695</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature, 2006-04, Vol.440 (7088), p.1222-1226 |
| issn | 0028-0836 1476-4687 1476-4679 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_35252832 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | Adhesion Animals Biological and medical sciences Blood vessels Breast cancer Cancer Cell Hypoxia Cell Line, Tumor Cell Movement - drug effects Clinical outcomes Complications and side effects Development and progression Disease Progression Dissemination Female Focal adhesion kinase Gynecology. Andrology. Obstetrics Head and neck Health aspects Humanities and Social Sciences Humans Hypoxia Hypoxia-inducible factors Inhibitor drugs Invasiveness Kinases letter Liquid oxygen Liver Neoplasms - drug therapy Liver Neoplasms - pathology Liver Neoplasms - secondary Lung Neoplasms - drug therapy Lung Neoplasms - pathology Lung Neoplasms - secondary Lysyl oxidase Mammary gland diseases Medical sciences Metastases Metastasis Mice Mice, Nude multidisciplinary Neoplasm Metastasis - drug therapy Neoplasm Metastasis - pathology Neoplasm Metastasis - physiopathology Neoplasm Transplantation Neoplasms - drug therapy Neoplasms - enzymology Neoplasms - metabolism Neoplasms - pathology Oncology Oxidase Oxidases Oxygen Oxygen requirement Physiological aspects Protein-Lysine 6-Oxidase - antagonists & inhibitors Protein-Lysine 6-Oxidase - metabolism Science Survival Rate Therapeutic applications Tumor cell Tumor microenvironment Tumorigenesis Tumors Vascularization |
| title | Lysyl oxidase is essential for hypoxia-induced metastasis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T21%3A27%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Lysyl%20oxidase%20is%20essential%20for%20hypoxia-induced%20metastasis&rft.jtitle=Nature&rft.au=Erler,%20Janine%20T.&rft.date=2006-04-27&rft.volume=440&rft.issue=7088&rft.spage=1222&rft.epage=1226&rft.pages=1222-1226&rft.issn=0028-0836&rft.eissn=1476-4687&rft.coden=NATUAS&rft_id=info:doi/10.1038/nature04695&rft_dat=%3Cgale_proqu%3EA185452127%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=204542049&rft_id=info:pmid/16642001&rft_galeid=A185452127&rfr_iscdi=true |