2. Academic Validation
  3. Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation

Fatty acid amide hydrolase drives adult mammary gland development by promoting luminal cell differentiation

  • Cell Death Discov. 2024 Jan 6;10(1):12. doi: 10.1038/s41420-023-01788-1.
Isabel Tundidor 1 2,  Marta Seijo-Vila 1 2,  Sandra Blasco-Benito 1 2,  María Rubert-Hernández 1 2,  Gema Moreno-Bueno 3,  Laura Bindila 4,  Rubén Fernández de la Rosa 5,  Manuel Guzmán 1 6,  Cristina Sánchez # 7 8,  Eduardo Pérez-Gómez # 9 10
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Complutense University, Madrid, Spain.
  • 2 Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain.
  • 3 MD 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), Madrid, Spain.
  • 4 Clinical Lipidomics Unit, Institute of Physiological Chemistry, University Medical Center, Mainz, Germany.
  • 5 Bioimagen Complutense (BIOIMAC), Complutense University, Madrid, Spain.
  • 6 Instituto Ramón y Cajal de Investigación Sanitaria and Centro de Investigación Sanitaria en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
  • 7 Department of Biochemistry and Molecular Biology, Complutense University, Madrid, Spain. [email protected].
  • 8 Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain. [email protected].
  • 9 Department of Biochemistry and Molecular Biology, Complutense University, Madrid, Spain. [email protected].
  • 10 Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain. [email protected].
  • # Contributed equally.
PMID: 38184644 DOI: 10.1038/s41420-023-01788-1
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.

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