Soluble ephrin a1 is necessary for the growth of HeLa and SK-BR3 cells.
Soluble ephrin a1 is necessary for the growth of HeLa and SK-BR3 cells.
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DOI：
10.1186/1475-2867-10-41
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发表时间：
2010-10-27
影响因子：
5.8
通讯作者：
Howard PL
中科院分区：
文献类型：
--
作者：
Alford S;Watson-Hurthig A;Scott N;Carette A;Lorimer H;Bazowski J;Howard PL
肝配蛋白A1（EFNA 1）是细胞表面蛋白A型肝配蛋白家族的成员，其作为A型Eph受体酪氨酸激酶家族的配体起作用。在恶性肿瘤中，EFNA 1及其首选受体EPHA 2的确切作用是有争议的。几项研究发现，EFNA 1可以抑制EPHA 2介导的肿瘤发生，或增强它，这取决于细胞类型和背景。然而，人们对影响EFNA 1促进或抑制致瘤性的条件知之甚少。EFNA 1以可溶形式以及糖磷脂酰肌醇（GPI）膜附着形式存在。我们研究了EFNA 1在恶性肿瘤中的矛盾作用是否可能部分与EFNA 1的可溶性和膜附着形式的存在以及它们与EPHA 2相互作用的方式的潜在差异有关。使用RNAi策略来降低内源性EFNA 1和EPHA 2的表达，我们发现EFNA 1和EPHA 2都是HeLa和SK-BR 3细胞生长所必需的。生长缺陷可以通过来自过表达可溶性EFNA 1的细胞的条件培养基来挽救。有趣的是，我们发现EFNA 1的膜附着形式的过表达在3D而不是2D中抑制HeLa细胞的生长。内源性EFNA 1的敲低或全长EFNA 1的过表达导致EPHA 2从细胞表面重新定位到细胞-细胞接触位点。可溶性EFNA 1的过表达导致更多的EPHA 2分布在细胞表面，远离细胞-细胞接触，并促进HeLa细胞的生长。我们得出结论，可溶性EFNA 1是必要的HeLa和SK-BR 3细胞的转化，并参与EPHA 2的重新定位远离网站的细胞-细胞接触转化过程中。
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. 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. 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.
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影响因子：
3.6
作者：
Hess, AR;Seftor, EA;Hendrix, MJC
通讯作者：
Hendrix, MJC
影响因子：
5.3
作者：
HOLZMAN, LB;MARKS, RM;DIXIT, VM
通讯作者：
DIXIT, VM
影响因子：
25
作者：
Himanen, JP;Chumley, MJ;Nikolov, DB
通讯作者：
Nikolov, DB
影响因子：
64.5
作者：
Dalva, MB;Takasu, MA;Greenberg, ME
通讯作者：
Greenberg, ME
DOI：
10.1073/pnas.78.5.3053
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
PEEHL, DM;STANBRIDGE, EJ
通讯作者：
STANBRIDGE, EJ