Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia.
Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia.
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DOI：
10.1083/jcb.201209151
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发表时间：
2013-04-15
期刊：
影响因子：
--
通讯作者：
Courtneidge SA
中科院分区：
文献类型：
--
作者：
Díaz B;Yuen A;Iizuka S;Higashiyama S;Courtneidge SA
Hypoxia increases the levels of ADAM12 in a Notch-dependent manner, leading to increased ectodomain shedding of HB-EGF and subsequent promotion of invadopodia formation. Notch regulates cell–cell contact-dependent signaling and is activated by hypoxia, a microenvironmental condition that promotes cellular invasion during both normal physiology and disease. The mechanisms by which hypoxia and Notch regulate cellular invasion are not fully elucidated. In this paper, we show that, in cancer cells, hypoxia increased the levels and activity of the ADAM12 metalloprotease in a Notch signaling–dependent manner, leading to increased ectodomain shedding of the epidermal growth factor (EGF) receptor (EGFR) ligand heparin-binding EGF-like growth factor. Released HB-EGF induced the formation of invadopodia, cellular structures that aid cancer cell invasion. Thus, we describe a signaling pathway that couples cell contact–dependent signaling with the paracrine activation of the EGFR, indicating cross talk between the Notch and EGFR pathways in promoting cancer cell invasion. This signaling pathway might regulate the coordinated acquisition of invasiveness by neighboring cells and mediate the communication between normoxic and hypoxic areas of tumors to facilitate cancer cell invasion.
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缺氧会增强乳腺癌中的 Notch 信号传导，导致 E-钙粘蛋白表达减少，细胞迁移和侵袭增加。
影响因子：
8.8
作者：
Chen, J.;Imanaka, N.;Chen, J.;Griffin, J. D.
通讯作者：
Griffin, J. D.
DOI：
10.1038/nrg3272
发表时间：
2012-09
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.5
作者：
Bravo-Cordero, Jose Javier;Hodgson, Louis;Condeelis, John
通讯作者：
Condeelis, John
影响因子：
4.6
作者：
Amarilio, Roy;Viukov, Sergey V.;Zelzer, Elazar
通讯作者：
Zelzer, Elazar
影响因子：
4.8
作者：
Abram, CL;Seals, DF;Courtneidge, SA
通讯作者：
Courtneidge, SA