1. Cell Biology
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G-protein-coupled receptor signaling and polarized actin dynamics drive cell-in-cell invasion

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Cite this article as: eLife 2014;3:e02786 doi: 10.7554/eLife.02786

Abstract

Homotypic or entotic cell-in-cell invasion is an integrin-independent process observed in carcinoma cells exposed during conditions of low adhesion such as in exudates of malignant disease. Although active cell-in-cell invasion depends on RhoA and actin the precise mechanism as well as the underlying actin structures and assembly factors driving the process are unknown. Furthermore, whether specific cell surface receptors trigger entotic invasion in a signal-dependent fashion has not been investigated. Here we identify the G-protein-coupled LPA receptor 2 (LPAR2) as a signal transducer specifically required for the actively invading cell during entosis. We find that G12/13 and PDZ-RhoGEF are required for entotic invasion, which is driven by blebbing and a uropod-like actin structure at the rear of the invading cell. Finally, we provide evidence for an involvement of the RhoA-regulated formin Dia1 for entosis downstream of LPAR2. Thus, we delineate a signaling process that regulates actin dynamics during cell-in-cell invasion.

Article and author information

Author details

  1. Vladimir Purvanov

    University of Marburg, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Manuel Holst

    University of Marburg, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Jameel Khan

    University of Marburg, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Christian Baarlink

    University of Marburg, Marburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Robert Grosse

    University of Marburg, Marburg, Germany
    For correspondence
    Robert.grosse@staff.uni-marburg.de
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. W James Nelson, Stanford University, United States

Publication history

  1. Received: March 14, 2014
  2. Accepted: June 19, 2014
  3. Accepted Manuscript published: June 20, 2014 (version 1)
  4. Version of Record published: July 15, 2014 (version 2)

Copyright

© 2014, Purvanov et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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