Soluble ephrin a1 is necessary for the growth of HeLa and SK-BR3 cells
Date
2010-10-27
Authors
Alford, Spencer
Watson-Hurthig, Adam
Scott, Nadia
Carette, Amanda
Lorimer, Heather
Bazowski, Jessa
Howard, Perry L.
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
Abstract
Background: Ephrin A1 (EFNA1) is a member of the A-type ephrin family of cell surface proteins that function as
ligands for the A-type Eph receptor tyrosine kinase family. In malignancy, the precise role of EFNA1 and its
preferred receptor, EPHA2, is controversial. Several studies have found that EFNA1 may suppress EPHA2-mediated
oncogenesis, or enhance it, depending on cell type and context. However, little is known about the conditions
that influence whether EFNA1 promotes or suppresses tumorigenicity. EFNA1 exists in a soluble form as well as a
glycophosphatidylinositol (GPI) membrane attached form. We investigated whether the contradictory roles of
EFNA1 in malignancy might in part be related to the existence of both soluble and membrane attached forms of
EFNA1 and potential differences in the manner in which they interact with EPHA2.
Results: Using a RNAi strategy to reduce the expression of endogenous EFNA1 and EPHA2, we found that both
EFNA1 and EPHA2 are required for growth of HeLa and SK-BR3 cells. The growth defects could be rescued by
conditioned media from cells overexpressing soluble EFNA1. Interestingly, we found that overexpression of the
membrane attached form of EFNA1 suppresses growth of HeLa cells in 3D but not 2D. Knockdown of endogenous
EFNA1, or overexpression of full-length EFNA1, resulted in relocalization of EPHA2 from the cell surface to sites of
cell-cell contact. Overexpression of soluble EFNA1 however resulted in more EPHA2 distributed on the cell surface,
away from cell-cell contacts, and promoted the growth of HeLa cells.
Conclusions: We conclude that soluble EFNA1 is necessary for the transformation of HeLa and SK-BR3 cells and
participates in the relocalization of EPHA2 away from sites of cell-cell contact during transformation.
Description
BioMed Central
Keywords
Centre for Biomedical Research
Citation
Alford et al.: Soluble ephrin a1 is necessary for the growth of HeLa and SK-BR3 cells. Cancer Cell International 2010 10:41.