N-WASP and cortactin are involved in invadopodium-dependent chemotaxis to EGF in breast tumor cells.
N-WASP and cortactin are involved in invadopodium-dependent chemotaxis to EGF in breast tumor cells.
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DOI：
10.1002/cm.20361
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发表时间：
2009-06
影响因子：
--
通讯作者：
Condeelis, John
中科院分区：
文献类型：
--
作者：
DesMarais, Vera;Yamaguchi, Hideki;Oser, Matthew;Soon, Lilian;Mouneimne, Ghassan;Sarmiento, Corina;Eddy, Robert;Condeelis, John
先前已观察到转移性乳腺癌细胞在厚的 ECM 基质上形成成熟的基质降解性侵袭伪足，而无需预先施加基质，则能够在玻璃上形成具有相似特征的侵袭伪足。它们响应 EGF 而形成，并含有常见的侵入足核心蛋白 N-WASP、Arp2/3、cortactin、cofilin 和 F-actin。对玻璃上侵袭伪足的研究允许进行更高分辨率的分析，包括使用全内反射显微镜并分析它们与其他细胞运动事件的关系，特别是片状伪足延伸和朝向 EGF 梯度的趋化性。在玻璃上形成侵入足需要 N-WASP 和 cortactin，但不需要微管。在 EGF 梯度中，在面向 EGF 源的细胞一侧形成更多的侵袭伪足。此外，N-WASP 或 cortactin 的消耗会阻止侵入足的形成，从而抑制细胞对 EGF 的趋化性。这似乎是趋化性的局部缺陷，因为通过 siRNA 消耗 N-WASP 或 cortactin 对片状足突出或片状足前缘处的倒刺末端生成没有影响。由于乳腺肿瘤细胞对 EGF 的趋化性参与了转移，因此抑制乳腺肿瘤细胞中的 N-WASP 活性可能会阻止肿瘤细胞的转移，同时不影响依赖于巨噬细胞中 WASp 功能的趋化依赖性先天免疫。
Metastatic mammary carcinoma cells, which have previously been observed to form mature, matrix degrading invadopodia on a thick ECM matrix, are able to form invadopodia with similar characteristics on glass without previously applied matrix. They form in response to EGF, and contain the usual invadopodium core proteins N-WASP, Arp2/3, cortactin, cofilin, and F-actin. The study of invadopodia on glass allows for higher resolution analysis including the use of total internal reflection microscopy and analysis of their relationship to other cell motility events, in particular, lamellipodium extension and chemotaxis toward an EGF gradient. Invadopodium formation on glass requires N-WASP and cortactin but not microtubules. In a gradient of EGF more invadopodia form on the side of the cells facing the source of EGF. In addition, depletion of N-WASP or cortactin, which blocks invadopodium fromation, inhibits chemotaxis of cells towards EGF. This appears to be a localized defect in chemotaxis since depletion of N-WASP or cortactin via siRNA had no effect on lamellipodium protrusion or barbed end generation at the lamellipodium's leading edge. Since chemotaxis to EGF by breast tumor cells is involved in metastasis, inhibiting N-WASP activity in breast tumor cells might prevent metastasis of tumor cells while not affecting chemotaxis-dependent innate immunity which depends on WASp function in macrophages.
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影响因子：
56.9
作者：
Ghosh, M;Song, XY;Condeelis, JS
通讯作者：
Condeelis, JS
影响因子：
4.8
作者：
Banzai, Y;Miki, H;Takenawa, T
通讯作者：
Takenawa, T
影响因子：
--
作者：
CHEN, WT
通讯作者：
CHEN, WT
DOI：
10.1083/jcb.148.3.531
发表时间：
2000-02-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chan AY;Bailly M;Zebda N;Segall JE;Condeelis JS
通讯作者：
Condeelis JS
影响因子：
8
作者：
Bowden, ET;Barth, M;Mueller, SC
通讯作者：
Mueller, SC