LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition
Summary Lysyl-oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family that catalyzes the cross-linking of collagens or elastins in the extracellular matrix, thus regulating the tensile strength of tissues. However, many reports have suggested different intracellular roles for LOXL2, including...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2014-01-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/3/2/129 |
| _version_ | 1818677965706231808 |
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| author | Eva P. Cuevas Gema Moreno-Bueno Giacomo Canesin Vanesa Santos Francisco Portillo Amparo Cano |
| author_facet | Eva P. Cuevas Gema Moreno-Bueno Giacomo Canesin Vanesa Santos Francisco Portillo Amparo Cano |
| author_sort | Eva P. Cuevas |
| collection | DOAJ |
| description | Summary
Lysyl-oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family that catalyzes the cross-linking of collagens or elastins in the extracellular matrix, thus regulating the tensile strength of tissues. However, many reports have suggested different intracellular roles for LOXL2, including the ability to regulate gene transcription and tumor progression. We previously reported that LOXL2 mediates epithelial-to-mesenchymal transition (EMT) by Snail1-dependent and independent mechanisms, related to E-cadherin silencing and downregulation of epidermal differentiation and cell polarity components, respectively. Whether or not the catalytic activity of LOXL2 is required to induce/sustain EMT is actually unknown. Here we show that LOXL2 catalytic inactive mutants collaborate with Snail1 in E-cadherin gene repression to trigger EMT and, in addition, promote FAK/Src pathway activation to support EMT. These findings reveal a non-conventional role of LOXL2 on regulating epithelial cell plasticity. |
| first_indexed | 2024-12-17T09:07:45Z |
| format | Article |
| id | doaj.art-065b6d60758d4f52ac0e7320d4895829 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-17T09:07:45Z |
| publishDate | 2014-01-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-065b6d60758d4f52ac0e7320d48958292022-12-21T21:55:23ZengThe Company of BiologistsBiology Open2046-63902014-01-013212913710.1242/bio.2014684120146841LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transitionEva P. Cuevas0Gema Moreno-Bueno1Giacomo Canesin2Vanesa Santos3Francisco Portillo4Amparo Cano5 Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM), IdiPAZ, 28029 Madrid, Spain Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM), IdiPAZ, 28029 Madrid, Spain Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM), IdiPAZ, 28029 Madrid, Spain Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM), IdiPAZ, 28029 Madrid, Spain Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM), IdiPAZ, 28029 Madrid, Spain Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM), IdiPAZ, 28029 Madrid, Spain Summary Lysyl-oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family that catalyzes the cross-linking of collagens or elastins in the extracellular matrix, thus regulating the tensile strength of tissues. However, many reports have suggested different intracellular roles for LOXL2, including the ability to regulate gene transcription and tumor progression. We previously reported that LOXL2 mediates epithelial-to-mesenchymal transition (EMT) by Snail1-dependent and independent mechanisms, related to E-cadherin silencing and downregulation of epidermal differentiation and cell polarity components, respectively. Whether or not the catalytic activity of LOXL2 is required to induce/sustain EMT is actually unknown. Here we show that LOXL2 catalytic inactive mutants collaborate with Snail1 in E-cadherin gene repression to trigger EMT and, in addition, promote FAK/Src pathway activation to support EMT. These findings reveal a non-conventional role of LOXL2 on regulating epithelial cell plasticity.http://bio.biologists.org/content/3/2/129LOXL2EMTLysyl oxidaseFAKSrc |
| spellingShingle | Eva P. Cuevas Gema Moreno-Bueno Giacomo Canesin Vanesa Santos Francisco Portillo Amparo Cano LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition Biology Open LOXL2 EMT Lysyl oxidase FAK Src |
| title | LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition |
| title_full | LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition |
| title_fullStr | LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition |
| title_full_unstemmed | LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition |
| title_short | LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition |
| title_sort | loxl2 catalytically inactive mutants mediate epithelial to mesenchymal transition |
| topic | LOXL2 EMT Lysyl oxidase FAK Src |
| url | http://bio.biologists.org/content/3/2/129 |
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