Here we study the effects of inducible oncogenic K-Ras (G12V) expression on the polarized morphogenesis of colonic epithelial cells. We provide evidence that the autocrine production of heregulins, ligands for the ErbB3 receptor tyrosine kinase, is responsible for the hyperproliferation and aberrant 3D morphogenesis upon oncogenic K-Ras expression. This is in line with results obtained in primary intestinal organoid cultures, in which exogenous heregulin is shown to interfere with normal tissue architecture. Importantly, ErbB3 inhibition and heregulin gene silencing rescued K-RasG12V-induced features of cell transformation. Together with the increased ErbB3 positivity detected in human high-grade primary colorectal cancers, our findings provide support for an autocrine signaling loop engaged by oncogenic K-Ras involving ErbB3 that contributes to the dedifferentiation of the intestinal epithelium during tumor initiation and progression.
%0 Journal Article
%1 Moller2016
%A Möller, Yvonne
%A Morkel, Markus
%A Schmid, Jens
%A Beyes, Sven
%A Hendrick, Janina
%A Strotbek, Michaela
%A Riemer, Pamela
%A Schmid, Simone
%A Schmitt, Lisa C
%A Kontermann, Roland
%A Mürdter, Thomas
%A Schwab, Matthias
%A Sers, Christine
%A Olayioye, Monilola a
%D 2016
%J Oncotarget
%K 2016 izi kontermann olayioye
%N 33
%P 53526--53539
%R 10.18632/oncotarget.10658
%T Oncogenic Ras triggers hyperproliferation and impairs polarized colonic morphogenesis by autocrine ErbB3 signaling.
%U https://doi.org/10.18632/oncotarget.10658
%V 7
%X Here we study the effects of inducible oncogenic K-Ras (G12V) expression on the polarized morphogenesis of colonic epithelial cells. We provide evidence that the autocrine production of heregulins, ligands for the ErbB3 receptor tyrosine kinase, is responsible for the hyperproliferation and aberrant 3D morphogenesis upon oncogenic K-Ras expression. This is in line with results obtained in primary intestinal organoid cultures, in which exogenous heregulin is shown to interfere with normal tissue architecture. Importantly, ErbB3 inhibition and heregulin gene silencing rescued K-RasG12V-induced features of cell transformation. Together with the increased ErbB3 positivity detected in human high-grade primary colorectal cancers, our findings provide support for an autocrine signaling loop engaged by oncogenic K-Ras involving ErbB3 that contributes to the dedifferentiation of the intestinal epithelium during tumor initiation and progression.
@article{Moller2016,
abstract = {Here we study the effects of inducible oncogenic K-Ras (G12V) expression on the polarized morphogenesis of colonic epithelial cells. We provide evidence that the autocrine production of heregulins, ligands for the ErbB3 receptor tyrosine kinase, is responsible for the hyperproliferation and aberrant 3D morphogenesis upon oncogenic K-Ras expression. This is in line with results obtained in primary intestinal organoid cultures, in which exogenous heregulin is shown to interfere with normal tissue architecture. Importantly, ErbB3 inhibition and heregulin gene silencing rescued K-RasG12V-induced features of cell transformation. Together with the increased ErbB3 positivity detected in human high-grade primary colorectal cancers, our findings provide support for an autocrine signaling loop engaged by oncogenic K-Ras involving ErbB3 that contributes to the dedifferentiation of the intestinal epithelium during tumor initiation and progression.},
added-at = {2023-06-29T13:07:55.000+0200},
author = {M{\"{o}}ller, Yvonne and Morkel, Markus and Schmid, Jens and Beyes, Sven and Hendrick, Janina and Strotbek, Michaela and Riemer, Pamela and Schmid, Simone and Schmitt, Lisa C and Kontermann, Roland and M{\"{u}}rdter, Thomas and Schwab, Matthias and Sers, Christine and Olayioye, Monilola a},
biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2dc9fefa46171f6a7b04f991818195b71/fabian},
doi = {10.18632/oncotarget.10658},
interhash = {32db979427f22ab19dfeac3d2a551809},
intrahash = {dc9fefa46171f6a7b04f991818195b71},
issn = {19492553},
journal = {Oncotarget},
keywords = {2016 izi kontermann olayioye},
month = aug,
number = 33,
pages = {53526--53539},
pmid = {27447549},
timestamp = {2023-06-29T13:07:55.000+0200},
title = {{Oncogenic Ras triggers hyperproliferation and impairs polarized colonic morphogenesis by autocrine ErbB3 signaling.}},
url = {https://doi.org/10.18632/oncotarget.10658},
volume = 7,
year = 2016
}