title: E-cadherin controls bronchiolar progenitor cells and onset of preneoplastic lesions in mice.
abstract: Although progenitor cells of the conducting airway have been spatially localized and some insights have been gained regarding their molecular phenotype, relatively little is known about the mechanisms regulating their maintenance, activation, and differentiation. This study investigates the potential roles of E-cadherin in mouse Clara cells, as these cells were shown to represent the progenitor/stem cells of the conducting airways and have been implicated as the cell of origin of human non-small cell lung cancer. Postnatal inactivation of E-cadherin affected Clara cell differentiation and compromised airway regeneration under injury conditions. In steady-state adult lung, overexpression of the dominant negative E-cadherin led to an expansion of the bronchiolar stem cells and decreased differentiation concomitant with canonical Wnt signaling activation. Expansion of the bronchiolar stem cell pool was associated with an incessant proliferation of neuroepithelial body.associated Clara cells that ultimately gave rise to bronchiolar hyperplasia. Despite progressive hyperplasia, only a minority of the mice developed pulmonary solid tumors, suggesting that the loss of E-cadherin function leads to tumor formation when additional mutations are sustained. The present study reveals that E-cadherin plays a critical role in the regulation of proliferation and homeostasis of the epithelial cells lining the conducting airways.
authors: Department of Molecular Biology, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors: Fatih
authors: F
authors: Ceteci
authors: Semra
authors: S
authors: Ceteci
authors: Emanuele
authors: E
authors: Zanucco
authors: Chitra
authors: C
authors: Thakur
authors: Matthias
authors: M
authors: Becker
authors: Nefertiti
authors: N
authors: El-Nikhely
authors: Ludger
authors: L
authors: Fink
authors: Werner
authors: W
authors: Seeger
authors: Rajkumar
authors: R
authors: Savai
authors: Ulf R
authors: UR
authors: Rapp
mesh_terms: D000818:Animals; D055745:Bronchioles / Q000378:metabolism* / Q000473:pathology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D006706:Homeostasis; D006965:Hyperplasia; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D012038:Regeneration; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D014598:Uteroglobin / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D015820:Cadherins; C556390:Scgb1a1 protein, mouse; D014598:Uteroglobin