Extracellular matrix regulates apoptosis in mammary epithelium through a control on insulin signaling.
Extracellular matrix regulates apoptosis in mammary epithelium through a control on insulin signaling.
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DOI：
10.1083/jcb.144.6.1337
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发表时间：
1999-03-22
期刊：
影响因子：
--
通讯作者：
Streuli CH
中科院分区：
文献类型：
--
作者：
Farrelly N;Lee YJ;Oliver J;Dive C;Streuli CH
粘附上皮细胞需要与细胞外基质相互作用才能生存，尽管其机制尚不明确。在原代乳腺上皮细胞的长期培养中，富含层粘连蛋白的基底膜（BM）而不是胶原I抑制细胞凋亡，表明粘附存活信号在其反应中是特异性的（.《细胞科学杂志》109：631-642）。我们现在证明来自BM的信号由整合素介导，并且需要α6和β1亚基。此外，来自胰岛素或胰岛素样生长因子的激素信号，而不是氢化可的松或催乳素，是抑制乳腺细胞凋亡所必需的，表明BM和可溶性因子在生存信号传导中合作。无论是在I型胶原或BM基质上培养的乳腺细胞，胰岛素均诱导其受体的自磷酸化。然而，胰岛素受体底物-1的酪氨酸磷酸化及其与磷脂酰肌醇3-激酶的结合在BM上培养的细胞中增强，磷脂酰肌醇3-激酶效应物蛋白激酶B的磷酸化也增强。这些结果表明，一种新的细胞外基质依赖性限制点在乳腺上皮细胞的胰岛素信号转导。胰岛素受体磷酸化的近端信号转导事件不依赖于细胞外基质，但下游效应物的激活需要与BM的粘附。由于磷脂酰肌醇3-激酶是乳腺上皮细胞存活所必需的，我们提出BM介导的细胞凋亡抑制的一种可能机制是通过其对胰岛素信号传导的促进作用。
Adherent epithelial cells require interactions with the extracellular matrix for their survival, though the mechanism is ill-defined. In long term cultures of primary mammary epithelial cells, a laminin-rich basement membrane (BM) but not collagen I suppresses apoptosis, indicating that adhesion survival signals are specific in their response (. J. Cell Sci. 109:631–642). We now demonstrate that the signal from BM is mediated by integrins and requires both the α6 and β1 subunits. In addition, a hormonal signal from insulin or insulin-like growth factors, but not hydrocortisone or prolactin, is necessary to suppress mammary cell apoptosis, indicating that BM and soluble factors cooperate in survival signaling. Insulin induced autophosphorylation of its receptor whether mammary cells were cultured on collagen I or BM substrata. However, both the tyrosine phosphorylation of insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase were enhanced in cells cultured on BM, as was the phosphorylation of the phosphatidylinositol 3-kinase effector, protein kinase B. These results suggest a novel extracellular matrix–dependent restriction point in insulin signaling in mammary epithelial cells. The proximal signal transduction event of insulin receptor phosphorylation is not dependent on extracellular matrix, but the activation of downstream effectors requires adhesion to BM. Since phosphatidylinositol 3-kinase was required for mammary epithelial cell survival, we propose that a possible mechanism for BM-mediated suppression of apoptosis is through its facilitative effects on insulin signaling.
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影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
7.5
作者：
Downward, J
通讯作者：
Downward, J
影响因子：
7.8
作者：
Frisch, SM;Vuori, K;Ruoslahti, E;ChanHui, PY
通讯作者：
ChanHui, PY
影响因子：
64.8
作者：
KauffmanZeh, A;RodriguezViciana, P;Evan, G
通讯作者：
Evan, G
DOI：
10.1083/jcb.124.4.619
发表时间：
1994-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Frisch SM;Francis H
通讯作者：
Francis H