Preclinical study reveals that PVRL4 drives anchorage-independent growth in breast cancer cells, indicating that antibody blockade of cell adhesion provides a targeted therapeutic strategy.
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. DOI:http://dx.doi.org/10.7554/eLife.00358.001.
No takes yet. Share an insight, caveat, or question.
Pavlova et al. (2013) studied this question.
Synapse has enriched one closely related paper. Consider it for comparative context: