Fine-tuning of Epithelial EGFR signals Supports Coordinated Mammary Gland Development - Archive ouverte HAL
Pré-Publication, Document De Travail Année : 2024

Fine-tuning of Epithelial EGFR signals Supports Coordinated Mammary Gland Development

Alexandr Samocha
  • Fonction : Auteur
Hanna Doh
  • Fonction : Auteur
Vaishnavi Sitarama
  • Fonction : Auteur
Quy H. Nguyen
  • Fonction : Auteur
Oghenekevwe M Gbenedio
Joshua Rudolf
  • Fonction : Auteur
Walter Eckalbar
  • Fonction : Auteur
Andrea Barczak
  • Fonction : Auteur
Yi Miao
K Christopher Garcia
  • Fonction : Auteur
Devon Lawson
Kai Kessenbrock
  • Fonction : Auteur
Jeroen Roose

Résumé

During puberty, robust morphogenesis occurs in the mammary gland; stem- and progenitor-cells develop into mature basal- and luminal-cells to form the ductal tree. The receptor signals that govern this process in mammary epithelial cells (MECs) are incompletely understood. The EGFR has been implicated and here we focused on EGFR’s downstream pathway component Rasgrp1. We find that Rasgrp1 dampens EGF-triggered signals in MECs. Biochemically and in vitro, Rasgrp1 perturbation results in increased EGFR-Ras-PI3K-AKT and mTORC1-S6 kinase signals, increased EGF-induced proliferation, and aberrant branching-capacity in 3D cultures. However, in vivo, Rasgrp1 perturbation results in delayed ductal tree maturation with shortened branches and reduced cellularity. Rasgrp1-deficient MEC organoids revealed lower frequencies of basal cells, the compartment that incorporates stem cells. Molecularly, EGF effectively counteracts Wnt signal-driven stem cell gene signature in organoids. Collectively, these studies demonstrate the need for fine-tuning of EGFR signals to properly instruct mammary epithelium during puberty.
Fichier principal
Vignette du fichier
2020.09.10.291872v1.full.pdf (15.52 Mo) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-04603841 , version 1 (19-07-2024)

Identifiants

Citer

Alexandr Samocha, Hanna Doh, Vaishnavi Sitarama, Quy H. Nguyen, Oghenekevwe M Gbenedio, et al.. Fine-tuning of Epithelial EGFR signals Supports Coordinated Mammary Gland Development. 2024. ⟨hal-04603841⟩

Collections

UNIV-MONTPELLIER
9 Consultations
3 Téléchargements

Altmetric

Partager

More