TY  - JOUR
A1  - Ceteci, Fatih
A1  - Ceteci, Semra
A1  - Zanucco, Emanuele
A1  - Thakur, Chitra
A1  - Becker, Matthias
A1  - El-Nikhely, Nefertiti
A1  - Fink, Ludger
A1  - Seeger, Werner
A1  - Savai, Rajkumar
A1  - Rapp, Ulf R.
T1  - E-Cadherin Controls Bronchiolar Progenitor Cells and Onset of Preneoplastic Lesions in Mice
T2  - Neoplasia
N2  - 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.
KW  - injury
KW  - lung cancer
KW  - stem cells
KW  - clara cell
KW  - gene expression
KW  - basal cell
KW  - in vivo
KW  - epithelium
KW  - airway
KW  - renewal
Y1  - 2012
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/13540
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-135407
VL  - 14
IS  - 12
ER  -