Location of Repository

A role for PVRL4-driven cell-cell interactions in tumorigenesis

By Christian Pallasch, Christian Joerg Braun, Michael Hemann, Natalya N. Pavlova, Andrew E. H. Elia, Thomas F. Westbrook and Stephen J. Elledge

Abstract

During all stages of tumor progression, cancer cells are subjected to inappropriate extracellular matrix environments and must undergo adaptive changes in order to evade growth constraints associated with the loss of matrix attachment. A gain of function screen for genes that enable proliferation independently of matrix anchorage identified a cell adhesion molecule PVRL4 (poliovirus-receptor-like 4), also known as Nectin-4. PVRL4 promotes anchorage-independence by driving cell-to-cell attachment and matrix-independent integrin β4/SHP-2/c-Src activation. Solid tumors frequently have copy number gains of the PVRL4 locus and some have focal amplifications. We demonstrate that the transformation of breast cancer cells is dependent on PVRL4. Furthermore, growth of orthotopically implanted tumors in vivo is inhibited by blocking PVRL4-driven cell-to-cell attachment with monoclonal antibodies, demonstrating a novel strategy for targeted therapy of cancer

Publisher: eLife Sciences Publications, Ltd.
Year: 2012
DOI identifier: 10.7554/eLife.00358
OAI identifier: oai:dspace.mit.edu:1721.1/84514
Provided by: DSpace@MIT
Journal:
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://hdl.handle.net/1721.1/8... (external link)
  • http://creativecommons.org/lic... (external link)
  • http://dx.doi.org/10.7554/eLif... (external link)
  • https://orcid.org/0000-0002-52... (external link)
  • http://purl.org/eprint/type/Jo... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.