A role for PVRL4-driven cell–cell interactions in tumorigenesis
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 30, 2013
- Source ID
- 10.7554/elife.00358
Entities
People
- Andrew Eh Elia
- Christian J Braun
- Christian Pallasch
- Michael Hemann
- Natalya N Pavlova
- Stephen Elledge
- Thomas F. Westbrook
Organizations
- Baylor College of Medicine
- Brigham and Women's Hospital
- Harvard Medical School
- Howard Hughes Medical Institute
- Massachusetts General Hospital
- Massachusetts Institute of Technology
- United States Department of Defense