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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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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 |
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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 |
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