Back to Search
Start Over
Progressive polarity loss and luminal collapse disrupt tissue organization in carcinoma
- Publication Year :
- 2017
- Publisher :
- Cold Spring Harbor Laboratory Press, 2017.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
RHOA
Polarity (physics)
Carcinogenesis
Primary Cell Culture
Morphogenesis
Fluorescent Antibody Technique
Breast Neoplasms
Biology
03 medical and health sciences
Mice
Cell polarity
Myosin
Genetics
Carcinoma
medicine
Animals
Humans
Cells, Cultured
Myosin Type II
Microscopy, Confocal
Cell Membrane
Cell Polarity
Anatomy
Apical membrane
medicine.disease
Cell biology
030104 developmental biology
biology.protein
Female
rhoA GTP-Binding Protein
Developmental Biology
Lumen (unit)
Research Paper
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....f6c63038cc4551ba010bc960efd1ca86