Rebalancing of actomyosin contractility enables mammary tumor formation upon loss of E-cadherin

Koen Schipper, Danielle Seinstra, Anne Paulien Drenth, Eline Burg, Veronika Ramovs, Arnoud Sonnenberg, Jacco Rheenen, Micha Nethe () and Jos Jonkers ()
Additional contact information
Koen Schipper: The Netherlands Cancer Institute
Danielle Seinstra: The Netherlands Cancer Institute
Anne Paulien Drenth: The Netherlands Cancer Institute
Eline Burg: The Netherlands Cancer Institute
Veronika Ramovs: The Netherlands Cancer Institute
Arnoud Sonnenberg: The Netherlands Cancer Institute
Jacco Rheenen: The Netherlands Cancer Institute
Micha Nethe: The Netherlands Cancer Institute
Jos Jonkers: The Netherlands Cancer Institute

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract E-cadherin (CDH1) is a master regulator of epithelial cell adherence junctions and a well-established tumor suppressor in Invasive Lobular Carcinoma (ILC). Intriguingly, somatic inactivation of E-cadherin alone in mouse mammary epithelial cells (MMECs) is insufficient to induce tumor formation. Here we show that E-cadherin loss induces extrusion of luminal MMECs to the basal lamina. Remarkably, E-cadherin-deficient MMECs can breach the basal lamina but do not disseminate into the surrounding fat pad. Basal lamina components laminin and collagen IV supported adhesion and survival of E-cadherin-deficient MMECs while collagen I, the principle component of the mammary stromal micro-environment did not. We uncovered that relaxation of actomyosin contractility mediates adhesion and survival of E-cadherin-deficient MMECs on collagen I, thereby allowing ILC development. Together, these findings unmask the direct consequences of E-cadherin inactivation in the mammary gland and identify aberrant actomyosin contractility as a critical barrier to ILC formation.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-11716-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11716-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-11716-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().