Lysyl oxidase-like 2 represses Notch1 expression in the skin to promote squamous cell carcinoma progression
Identifieur interne : 002B75 ( Main/Exploration ); précédent : 002B74; suivant : 002B76Lysyl oxidase-like 2 represses Notch1 expression in the skin to promote squamous cell carcinoma progression
Auteurs : Alberto Martin [Espagne] ; Fernando Salvador [Espagne] ; Gema Moreno-Bueno [Espagne] ; Alfredo Floristán [Espagne] ; Cristina Ruiz-Herguido [Espagne] ; Eva P. Cuevas [Espagne] ; Saleta Morales [Espagne] ; Vanesa Santos [Espagne] ; Katalin Csiszar [États-Unis] ; Pierre Dubus [France] ; Jody J. Haigh [Australie] ; Anna Bigas [Espagne] ; Francisco Portillo [Espagne] ; Amparo Cano [Espagne]Source :
- The EMBO Journal [ 0261-4189 ] ; 2015.
Descripteurs français
- KwdFr :
- Amino-acid oxidoreductases (génétique), Amino-acid oxidoreductases (physiologie), Animaux, Animaux nouveau-nés, Carcinome épidermoïde (anatomopathologie), Carcinome épidermoïde (génétique), Cellules HEK293, Cellules cultivées, Femelle, Humains, Mâle, Récepteur Notch1 (génétique), Régulation de l'expression des gènes tumoraux, Régulation négative, Souris, Souris knockout, Transformation cellulaire néoplasique (génétique), Tumeurs cutanées (anatomopathologie), Tumeurs cutanées (génétique), Tumeurs de la tête et du cou (anatomopathologie), Tumeurs de la tête et du cou (génétique), Évolution de la maladie.
- MESH :
- anatomopathologie : Carcinome épidermoïde, Tumeurs cutanées, Tumeurs de la tête et du cou.
- génétique : Amino-acid oxidoreductases, Carcinome épidermoïde, Récepteur Notch1, Transformation cellulaire néoplasique, Tumeurs cutanées, Tumeurs de la tête et du cou.
- physiologie : Amino-acid oxidoreductases.
- Animaux, Animaux nouveau-nés, Cellules HEK293, Cellules cultivées, Femelle, Humains, Mâle, Régulation de l'expression des gènes tumoraux, Régulation négative, Souris, Souris knockout, Évolution de la maladie.
English descriptors
- KwdEn :
- Amino Acid Oxidoreductases (genetics), Amino Acid Oxidoreductases (physiology), Animals, Animals, Newborn, Carcinoma, Squamous Cell (genetics), Carcinoma, Squamous Cell (pathology), Cell Transformation, Neoplastic (genetics), Cells, Cultured, Disease Progression, Down-Regulation, Female, Gene Expression Regulation, Neoplastic, HEK293 Cells, Head and Neck Neoplasms (genetics), Head and Neck Neoplasms (pathology), Humans, Male, Mice, Mice, Knockout, Receptor, Notch1 (genetics), Skin Neoplasms (genetics), Skin Neoplasms (pathology).
- MESH :
- chemical , genetics : Amino Acid Oxidoreductases, Receptor, Notch1.
- chemical , physiology : Amino Acid Oxidoreductases.
- genetics : Carcinoma, Squamous Cell, Cell Transformation, Neoplastic, Head and Neck Neoplasms, Skin Neoplasms.
- pathology : Carcinoma, Squamous Cell, Head and Neck Neoplasms, Skin Neoplasms.
- Animals, Animals, Newborn, Cells, Cultured, Disease Progression, Down-Regulation, Female, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Male, Mice, Mice, Knockout.
Abstract
Lysyl oxidase-like 2 (LOXL2) is involved in a wide range of physiological and pathological processes, including fibrosis and tumor progression, implicating intracellular and extracellular functions. To explore the specific
Url:
DOI: 10.15252/embj.201489975
PubMed: 25759215
PubMed Central: 4406654
Affiliations:
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Le document en format XML
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xml:lang="fr">Espagne</country><wicri:regionArea>Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Salvador, Fernando" sort="Salvador, Fernando" uniqKey="Salvador F" first="Fernando" last="Salvador">Fernando Salvador</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM, IdiPAZ</institution><addr-line>Madrid, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Moreno Bueno, Gema" sort="Moreno Bueno, Gema" uniqKey="Moreno Bueno G" first="Gema" last="Moreno-Bueno">Gema Moreno-Bueno</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM, IdiPAZ</institution><addr-line>Madrid, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Madrid</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="au2"><institution>Fundación MD Anderson International Madrid</institution><addr-line>Madrid, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Floristan, Alfredo" sort="Floristan, Alfredo" uniqKey="Floristan A" first="Alfredo" last="Floristán">Alfredo Floristán</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM, IdiPAZ</institution><addr-line>Madrid, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Ruiz Herguido, Cristina" sort="Ruiz Herguido, Cristina" uniqKey="Ruiz Herguido C" first="Cristina" last="Ruiz-Herguido">Cristina Ruiz-Herguido</name><affiliation wicri:level="1"><nlm:aff id="au3"><institution>Institut Hospital del Mar d'Investigacions Médiques (IMIM)</institution><addr-line>Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Cuevas, Eva P" sort="Cuevas, Eva P" uniqKey="Cuevas E" first="Eva P" last="Cuevas">Eva P. Cuevas</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM, IdiPAZ</institution><addr-line>Madrid, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Morales, Saleta" sort="Morales, Saleta" uniqKey="Morales S" first="Saleta" last="Morales">Saleta Morales</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM, IdiPAZ</institution><addr-line>Madrid, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Santos, Vanesa" sort="Santos, Vanesa" uniqKey="Santos V" first="Vanesa" last="Santos">Vanesa Santos</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM, IdiPAZ</institution><addr-line>Madrid, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Csiszar, Katalin" sort="Csiszar, Katalin" uniqKey="Csiszar K" first="Katalin" last="Csiszar">Katalin Csiszar</name><affiliation wicri:level="2"><nlm:aff id="au4"><institution>John A Burns School of Medicine, University of Hawaii</institution><addr-line>Honolulu, HI, USA</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Honolulu, HI</wicri:regionArea><placeName><region type="state">Hawaï</region></placeName></affiliation></author><author><name sortKey="Dubus, Pierre" sort="Dubus, Pierre" uniqKey="Dubus P" first="Pierre" last="Dubus">Pierre Dubus</name><affiliation wicri:level="1"><nlm:aff id="au5"><institution>Histologie et pathologie moléculaire des tumeurs, Universitie Bordeaux</institution><addr-line>Bordeaux, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Haigh, Jody J" sort="Haigh, Jody J" uniqKey="Haigh J" first="Jody J" last="Haigh">Jody J. Haigh</name><affiliation wicri:level="1"><nlm:aff id="au6"><institution>Australian Centre for Blood Diseases, Monash University</institution><addr-line>Melbourne, Vic., Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Melbourne, Vic.</wicri:regionArea><wicri:noRegion>Vic.</wicri:noRegion></affiliation></author><author><name sortKey="Bigas, Anna" sort="Bigas, Anna" uniqKey="Bigas A" first="Anna" last="Bigas">Anna Bigas</name><affiliation wicri:level="1"><nlm:aff id="au3"><institution>Institut Hospital del Mar d'Investigacions Médiques (IMIM)</institution><addr-line>Barcelona, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Portillo, Francisco" sort="Portillo, Francisco" uniqKey="Portillo F" first="Francisco" last="Portillo">Francisco Portillo</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM, IdiPAZ</institution><addr-line>Madrid, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Madrid</wicri:regionArea></affiliation></author><author><name sortKey="Cano, Amparo" sort="Cano, Amparo" uniqKey="Cano A" first="Amparo" last="Cano">Amparo Cano</name><affiliation wicri:level="1"><nlm:aff id="au1"><institution>Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC-UAM, IdiPAZ</institution><addr-line>Madrid, Spain</addr-line></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea>Madrid</wicri:regionArea></affiliation></author></analytic><series><title level="j">The EMBO Journal</title><idno type="ISSN">0261-4189</idno><idno type="eISSN">1460-2075</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Oxidoreductases (genetics)</term><term>Amino Acid Oxidoreductases (physiology)</term><term>Animals</term><term>Animals, Newborn</term><term>Carcinoma, Squamous Cell (genetics)</term><term>Carcinoma, Squamous Cell (pathology)</term><term>Cell Transformation, Neoplastic (genetics)</term><term>Cells, Cultured</term><term>Disease Progression</term><term>Down-Regulation</term><term>Female</term><term>Gene Expression Regulation, Neoplastic</term><term>HEK293 Cells</term><term>Head and Neck Neoplasms (genetics)</term><term>Head and Neck Neoplasms (pathology)</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Knockout</term><term>Receptor, Notch1 (genetics)</term><term>Skin Neoplasms (genetics)</term><term>Skin Neoplasms (pathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Amino-acid oxidoreductases (génétique)</term><term>Amino-acid oxidoreductases (physiologie)</term><term>Animaux</term><term>Animaux nouveau-nés</term><term>Carcinome épidermoïde (anatomopathologie)</term><term>Carcinome épidermoïde (génétique)</term><term>Cellules HEK293</term><term>Cellules cultivées</term><term>Femelle</term><term>Humains</term><term>Mâle</term><term>Récepteur Notch1 (génétique)</term><term>Régulation de l'expression des gènes tumoraux</term><term>Régulation négative</term><term>Souris</term><term>Souris knockout</term><term>Transformation cellulaire néoplasique (génétique)</term><term>Tumeurs cutanées (anatomopathologie)</term><term>Tumeurs cutanées (génétique)</term><term>Tumeurs de la tête et du cou (anatomopathologie)</term><term>Tumeurs de la tête et du cou (génétique)</term><term>Évolution de la maladie</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Amino Acid Oxidoreductases</term><term>Receptor, Notch1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Amino Acid Oxidoreductases</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Carcinome épidermoïde</term><term>Tumeurs cutanées</term><term>Tumeurs de la tête et du cou</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Carcinoma, Squamous Cell</term><term>Cell Transformation, Neoplastic</term><term>Head and Neck Neoplasms</term><term>Skin Neoplasms</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Amino-acid oxidoreductases</term><term>Carcinome épidermoïde</term><term>Récepteur Notch1</term><term>Transformation cellulaire néoplasique</term><term>Tumeurs cutanées</term><term>Tumeurs de la tête et du cou</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Carcinoma, Squamous Cell</term><term>Head and Neck Neoplasms</term><term>Skin Neoplasms</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Amino-acid oxidoreductases</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Animals, Newborn</term><term>Cells, Cultured</term><term>Disease Progression</term><term>Down-Regulation</term><term>Female</term><term>Gene Expression Regulation, Neoplastic</term><term>HEK293 Cells</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Knockout</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Animaux nouveau-nés</term><term>Cellules HEK293</term><term>Cellules cultivées</term><term>Femelle</term><term>Humains</term><term>Mâle</term><term>Régulation de l'expression des gènes tumoraux</term><term>Régulation négative</term><term>Souris</term><term>Souris knockout</term><term>Évolution de la maladie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Lysyl oxidase-like 2 (LOXL2) is involved in a wide range of physiological and pathological processes, including fibrosis and tumor progression, implicating intracellular and extracellular functions. To explore the specific <italic>in vivo</italic> role of LOXL2 in physiological and tumor contexts, we generated conditional gain- and loss-of-function mouse models. Germ-line deletion of <italic>Loxl2</italic> promotes lethality in half of newborn mice mainly associated to congenital heart defects, while <italic>Loxl2</italic> overexpression triggers male sterility due to epididymal dysfunction caused by epithelial disorganization, fibrosis and acute inflammation. Remarkably, when challenged to chemical skin carcinogenesis, <italic>Loxl2-</italic>overexpressing mice increased tumor burden and malignant progression, while <italic>Loxl2</italic>-deficient mice exhibit the opposite phenotypes. Loxl2 levels in premalignant tumors negatively correlate with expression of epidermal differentiation markers and components of the Notch1 pathway. We show that LOXL2 is a direct repressor of <italic>NOTCH1</italic>. Additionally, we identify an exclusive expression pattern between LOXL2 and members of the canonical NOTCH1 pathway in human HNSCC. Our data identify for the first time novel LOXL2 roles in tissue homeostasis and support it as a target for SCC therapy.</p></div></front></TEI><affiliations><list><country><li>Australie</li><li>Espagne</li><li>France</li><li>États-Unis</li></country><region><li>Hawaï</li></region></list><tree><country name="Espagne"><noRegion><name sortKey="Martin, Alberto" sort="Martin, Alberto" uniqKey="Martin A" first="Alberto" last="Martin">Alberto Martin</name></noRegion><name sortKey="Bigas, Anna" sort="Bigas, Anna" uniqKey="Bigas A" first="Anna" last="Bigas">Anna Bigas</name><name sortKey="Cano, Amparo" sort="Cano, Amparo" uniqKey="Cano A" first="Amparo" last="Cano">Amparo Cano</name><name sortKey="Cuevas, Eva P" sort="Cuevas, Eva P" uniqKey="Cuevas E" first="Eva P" last="Cuevas">Eva P. Cuevas</name><name sortKey="Floristan, Alfredo" sort="Floristan, Alfredo" uniqKey="Floristan A" first="Alfredo" last="Floristán">Alfredo Floristán</name><name sortKey="Morales, Saleta" sort="Morales, Saleta" uniqKey="Morales S" first="Saleta" last="Morales">Saleta Morales</name><name sortKey="Moreno Bueno, Gema" sort="Moreno Bueno, Gema" uniqKey="Moreno Bueno G" first="Gema" last="Moreno-Bueno">Gema Moreno-Bueno</name><name sortKey="Moreno Bueno, Gema" sort="Moreno Bueno, Gema" uniqKey="Moreno Bueno G" first="Gema" last="Moreno-Bueno">Gema Moreno-Bueno</name><name sortKey="Portillo, Francisco" sort="Portillo, Francisco" uniqKey="Portillo F" first="Francisco" last="Portillo">Francisco Portillo</name><name sortKey="Ruiz Herguido, Cristina" sort="Ruiz Herguido, Cristina" uniqKey="Ruiz Herguido C" first="Cristina" last="Ruiz-Herguido">Cristina Ruiz-Herguido</name><name sortKey="Salvador, Fernando" sort="Salvador, Fernando" uniqKey="Salvador F" first="Fernando" last="Salvador">Fernando Salvador</name><name sortKey="Santos, Vanesa" sort="Santos, Vanesa" uniqKey="Santos V" first="Vanesa" last="Santos">Vanesa Santos</name></country><country name="États-Unis"><region name="Hawaï"><name sortKey="Csiszar, Katalin" sort="Csiszar, Katalin" uniqKey="Csiszar K" first="Katalin" last="Csiszar">Katalin Csiszar</name></region></country><country name="France"><noRegion><name sortKey="Dubus, Pierre" sort="Dubus, Pierre" uniqKey="Dubus P" first="Pierre" last="Dubus">Pierre Dubus</name></noRegion></country><country name="Australie"><noRegion><name sortKey="Haigh, Jody J" sort="Haigh, Jody J" uniqKey="Haigh J" first="Jody J" last="Haigh">Jody J. 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