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

Koen Schipper, Danielle Seinstra, Anne Paulien Drenth, Eline van der Burg, Veronika Ramovs, Arnoud Sonnenberg, Jacco van Rheenen, Micha Nethe, Jos Jonkers

Nature communications 2019 Aug 23

filter terms:

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.

Citation

Koen Schipper, Danielle Seinstra, Anne Paulien Drenth, Eline van der Burg, Veronika Ramovs, Arnoud Sonnenberg, Jacco van Rheenen, Micha Nethe, Jos Jonkers. Rebalancing of actomyosin contractility enables mammary tumor formation upon loss of E-cadherin. Nature communications. 2019 Aug 23;10(1):3800