Cargando…

Progressive polarity loss and luminal collapse disrupt tissue organization in carcinoma

Epithelial cancers (carcinoma) account for 80%–90% of all cancers. The development of carcinoma is associated with disrupted epithelial organization and solid ductal structures. The mechanisms underlying the morphological development of carcinoma are poorly understood, but it is thought that loss of...

Descripción completa

Detalles Bibliográficos
Autores principales: Halaoui, Ruba, Rejon, Carlis, Chatterjee, Sudipa June, Szymborski, Joseph, Meterissian, Sarkis, Muller, William J., Omeroglu, Atilla, McCaffrey, Luke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630022/
https://www.ncbi.nlm.nih.gov/pubmed/28887414
http://dx.doi.org/10.1101/gad.300566.117
_version_ 1783269159608516608
author Halaoui, Ruba
Rejon, Carlis
Chatterjee, Sudipa June
Szymborski, Joseph
Meterissian, Sarkis
Muller, William J.
Omeroglu, Atilla
McCaffrey, Luke
author_facet Halaoui, Ruba
Rejon, Carlis
Chatterjee, Sudipa June
Szymborski, Joseph
Meterissian, Sarkis
Muller, William J.
Omeroglu, Atilla
McCaffrey, Luke
author_sort Halaoui, Ruba
collection PubMed
description Epithelial cancers (carcinoma) account for 80%–90% of all cancers. The development of carcinoma is associated with disrupted epithelial organization and solid ductal structures. The mechanisms underlying the morphological development of carcinoma are poorly understood, but it is thought that loss of cell polarity is an early event. Here we report the characterization of the development of human breast lesions leading to carcinoma. We identified a unique mechanism that generates solid ducts in carcinoma through progressive loss of polarity and collapse of the luminal architecture. This program initiates with asymmetric divisions of polarized cells that generate a stratified epithelium containing both polarized and depolarized cells. Stratified regions form cords that penetrate into the lumen, subdividing it into polarized secondary lumina. The secondary lumina then collapse with a concomitant decrease in RhoA and myosin II activity at the apical membrane and ultimately lose apical–basal polarity. By restoring RhoA activity in mice, ducts maintained lumen and cell polarity. Notably, disrupted tissue architecture through luminal collapse was reversible, and ducts with a lumen were re-established after oncogene suppression in vivo. This reveals a novel and common mechanism that contributes to carcinoma development by progressively disrupting cell and tissue organization.
format Online
Article
Text
id pubmed-5630022
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-56300222018-02-01 Progressive polarity loss and luminal collapse disrupt tissue organization in carcinoma Halaoui, Ruba Rejon, Carlis Chatterjee, Sudipa June Szymborski, Joseph Meterissian, Sarkis Muller, William J. Omeroglu, Atilla McCaffrey, Luke Genes Dev Research Paper Epithelial cancers (carcinoma) account for 80%–90% of all cancers. The development of carcinoma is associated with disrupted epithelial organization and solid ductal structures. The mechanisms underlying the morphological development of carcinoma are poorly understood, but it is thought that loss of cell polarity is an early event. Here we report the characterization of the development of human breast lesions leading to carcinoma. We identified a unique mechanism that generates solid ducts in carcinoma through progressive loss of polarity and collapse of the luminal architecture. This program initiates with asymmetric divisions of polarized cells that generate a stratified epithelium containing both polarized and depolarized cells. Stratified regions form cords that penetrate into the lumen, subdividing it into polarized secondary lumina. The secondary lumina then collapse with a concomitant decrease in RhoA and myosin II activity at the apical membrane and ultimately lose apical–basal polarity. By restoring RhoA activity in mice, ducts maintained lumen and cell polarity. Notably, disrupted tissue architecture through luminal collapse was reversible, and ducts with a lumen were re-established after oncogene suppression in vivo. This reveals a novel and common mechanism that contributes to carcinoma development by progressively disrupting cell and tissue organization. Cold Spring Harbor Laboratory Press 2017-08-01 /pmc/articles/PMC5630022/ /pubmed/28887414 http://dx.doi.org/10.1101/gad.300566.117 Text en © 2017 Halaoui et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Halaoui, Ruba
Rejon, Carlis
Chatterjee, Sudipa June
Szymborski, Joseph
Meterissian, Sarkis
Muller, William J.
Omeroglu, Atilla
McCaffrey, Luke
Progressive polarity loss and luminal collapse disrupt tissue organization in carcinoma
title Progressive polarity loss and luminal collapse disrupt tissue organization in carcinoma
title_full Progressive polarity loss and luminal collapse disrupt tissue organization in carcinoma
title_fullStr Progressive polarity loss and luminal collapse disrupt tissue organization in carcinoma
title_full_unstemmed Progressive polarity loss and luminal collapse disrupt tissue organization in carcinoma
title_short Progressive polarity loss and luminal collapse disrupt tissue organization in carcinoma
title_sort progressive polarity loss and luminal collapse disrupt tissue organization in carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630022/
https://www.ncbi.nlm.nih.gov/pubmed/28887414
http://dx.doi.org/10.1101/gad.300566.117
work_keys_str_mv AT halaouiruba progressivepolaritylossandluminalcollapsedisrupttissueorganizationincarcinoma
AT rejoncarlis progressivepolaritylossandluminalcollapsedisrupttissueorganizationincarcinoma
AT chatterjeesudipajune progressivepolaritylossandluminalcollapsedisrupttissueorganizationincarcinoma
AT szymborskijoseph progressivepolaritylossandluminalcollapsedisrupttissueorganizationincarcinoma
AT meterissiansarkis progressivepolaritylossandluminalcollapsedisrupttissueorganizationincarcinoma
AT mullerwilliamj progressivepolaritylossandluminalcollapsedisrupttissueorganizationincarcinoma
AT omerogluatilla progressivepolaritylossandluminalcollapsedisrupttissueorganizationincarcinoma
AT mccaffreyluke progressivepolaritylossandluminalcollapsedisrupttissueorganizationincarcinoma