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mDia2 formin selectively interacts with catenins and not E-cadherin to regulate Adherens Junction formation

Yuqi Zhang,Krista M. Pettee,Kathryn N. Becker,Kathryn M. Eisenmann

Published 2019 in bioRxiv

ABSTRACT

Background Epithelial ovarian cancer (EOC) cells disseminate within the peritoneal cavity, in part, via the peritoneal fluid as single cells, clusters, or spheroids. Initial single cell egress from a tumor can involve disruption of cell-cell adhesions as cells are shed from the primary tumor into the peritoneum. In epithelial cells, Adherens Junctions (AJs) are characterized by homotypic linkage of E-cadherins on the plasma membranes of adjacent cells. AJs are anchored to the intracellular actin cytoskeletal network through a complex involving E-cadherin, p120 catenin, β-catenin, and αE-catenin. However, the specific players involved in the interaction between the junctional E-cadherin complex and the underlying F-actin network remains unclear. Recent evidence indicates that mammalian Diaphanous-related (mDia) formins plays a key role in epithelial cell AJ formation and maintenance through generation of linear actin filaments. Binding of αE-catenin to linear F-actin inhibits association of the branched-actin nucleator Arp2/3, while favoring linear F-actin bundling. We previously demonstrated that loss of mDia2 was associated with invasive single cell egress from EOC spheroids through disruption of junctional F-actin. Results In the current study, we now show that mDia2 has a role at adherens junctions (AJs) in EOC OVCA429 cells and human embryonic kidney (HEK) 293 cells through its association with αE-catenin and β-catenin. mDia2 depletion in EOC cells leads to reduction in actin polymerization and disruption of cell-cell junctions with decreased interaction between β-catenin and E-cadherin. Conclusions Our results support a necessary role for mDia2 in AJ stability in EOC cell monolayers and indicate a critical role for mDia formins in regulating EOC AJs during invasive transitions.

PUBLICATION RECORD

  • Publication year

    2019

  • Venue

    bioRxiv

  • Publication date

    2019-08-01

  • Fields of study

    Biology, Medicine, Chemistry

  • Identifiers
    DOI 10.1101/721530
  • External record

    Open on Semantic Scholar

  • Source metadata

    Semantic Scholar

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