Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation
Abstract Mammary gland development occurs primarily in adulthood, undergoing extensive expansion during puberty followed by cycles of functional specialization and regression with every round of pregnancy/lactation/involution. This process is ultimately driven by the coordinated proliferation and di...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-01-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01788-1 |
| _version_ | 1827388732005679104 |
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| author | Isabel Tundidor Marta Seijo-Vila Sandra Blasco-Benito María Rubert-Hernández Gema Moreno-Bueno Laura Bindila Rubén Fernández de la Rosa Manuel Guzmán Cristina Sánchez Eduardo Pérez-Gómez |
| author_facet | Isabel Tundidor Marta Seijo-Vila Sandra Blasco-Benito María Rubert-Hernández Gema Moreno-Bueno Laura Bindila Rubén Fernández de la Rosa Manuel Guzmán Cristina Sánchez Eduardo Pérez-Gómez |
| author_sort | Isabel Tundidor |
| collection | DOAJ |
| description | Abstract Mammary gland development occurs primarily in adulthood, undergoing extensive expansion during puberty followed by cycles of functional specialization and regression with every round of pregnancy/lactation/involution. This process is ultimately driven by the coordinated proliferation and differentiation of mammary epithelial cells. However, the endogenous molecular factors regulating these developmental dynamics are still poorly defined. Endocannabinoid signaling is known to determine cell fate-related events during the development of different organs in the central nervous system and the periphery. Here, we report that the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) plays a pivotal role in adult mammary gland development. Specifically, it is required for luminal lineage specification in the mammary gland, and it promotes hormone-driven secretory differentiation of mammary epithelial cells by controlling the endogenous levels of anandamide and the subsequent activation of cannabinoid CB1 receptors. Together, our findings shed light on the role of the endocannabinoid system in breast development and point to FAAH as a therapeutic target in milk-production deficits. |
| first_indexed | 2024-03-08T16:23:11Z |
| format | Article |
| id | doaj.art-3d512f49edd5494f82227c64f367f738 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-03-08T16:23:11Z |
| publishDate | 2024-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-3d512f49edd5494f82227c64f367f7382024-01-07T12:11:22ZengNature Publishing GroupCell Death Discovery2058-77162024-01-0110111210.1038/s41420-023-01788-1Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiationIsabel Tundidor0Marta Seijo-Vila1Sandra Blasco-Benito2María Rubert-Hernández3Gema Moreno-Bueno4Laura Bindila5Rubén Fernández de la Rosa6Manuel Guzmán7Cristina Sánchez8Eduardo Pérez-Gómez9Department of Biochemistry and Molecular Biology, Complutense UniversityDepartment of Biochemistry and Molecular Biology, Complutense UniversityDepartment of Biochemistry and Molecular Biology, Complutense UniversityDepartment of Biochemistry and Molecular Biology, Complutense UniversityMD Anderson International Foundation; Department of Biochemistry, Autonomous University of Madrid; Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM); Instituto de Investigación Hospital Universitario La Paz (IdiPAZ); Centro de Investigación Biomédica en Red de Cáncer (CIBERONC)Clinical Lipidomics Unit, Institute of Physiological Chemistry, University Medical CenterBioimagen Complutense (BIOIMAC), Complutense UniversityDepartment of Biochemistry and Molecular Biology, Complutense UniversityDepartment of Biochemistry and Molecular Biology, Complutense UniversityDepartment of Biochemistry and Molecular Biology, Complutense UniversityAbstract Mammary gland development occurs primarily in adulthood, undergoing extensive expansion during puberty followed by cycles of functional specialization and regression with every round of pregnancy/lactation/involution. This process is ultimately driven by the coordinated proliferation and differentiation of mammary epithelial cells. However, the endogenous molecular factors regulating these developmental dynamics are still poorly defined. Endocannabinoid signaling is known to determine cell fate-related events during the development of different organs in the central nervous system and the periphery. Here, we report that the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) plays a pivotal role in adult mammary gland development. Specifically, it is required for luminal lineage specification in the mammary gland, and it promotes hormone-driven secretory differentiation of mammary epithelial cells by controlling the endogenous levels of anandamide and the subsequent activation of cannabinoid CB1 receptors. Together, our findings shed light on the role of the endocannabinoid system in breast development and point to FAAH as a therapeutic target in milk-production deficits.https://doi.org/10.1038/s41420-023-01788-1 |
| spellingShingle | Isabel Tundidor Marta Seijo-Vila Sandra Blasco-Benito María Rubert-Hernández Gema Moreno-Bueno Laura Bindila Rubén Fernández de la Rosa Manuel Guzmán Cristina Sánchez Eduardo Pérez-Gómez Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation Cell Death Discovery |
| title | Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation |
| title_full | Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation |
| title_fullStr | Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation |
| title_full_unstemmed | Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation |
| title_short | Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation |
| title_sort | fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation |
| url | https://doi.org/10.1038/s41420-023-01788-1 |
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