An invasion-related complex of cortactin, paxillin and PKCμ associates with invadopodia at sites of extracellular matrix degradation
An invasion-related complex of cortactin, paxillin and PKCμ associates with invadopodia at sites of extracellular matrix degradation
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DOI：
10.1038/sj.onc.1202827
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发表时间：
1999-08-05
期刊：
影响因子：
8
通讯作者：
Mueller, SC
中科院分区：
文献类型：
--
作者：
Bowden, ET;Barth, M;Mueller, SC
浸润性乳腺癌细胞具有扩展膜突（侵过性）进入细胞外基质（EC）的能力。这些结构与活性基质降解位点有关。与这些膜突起活动相关的基质降解量已被证明与侵入电位直接相关。我们在这里证明，微注射多克隆抗接触蛋白抗体阻断了基质在侵入性动物的降解，这支持了接触蛋白在侵入性行为中有直接作用的假设。从明胶基质表面剪切MDA-MB-231浸润性乳腺癌细胞，分离侵足。皮坦、帕罗西林和蛋白激酶C (PKC) mu（一种丝氨酸激酶）作为复合物从侵入过继体富集膜上共免疫沉淀。我们通过免疫定位和Western blotting证实了这些蛋白的亚细胞分布。我们还确定，与它在侵入性细胞中的存在相反，这种蛋白质复合物在不形成侵入性的非侵入性细胞的裂解物中未被检测到。综上所述，这些数据表明这种含接触蛋白复合物的形成与细胞侵袭性相关。我们假设这种分子复合物在细胞侵袭过程中参与了侵殖体的形成和功能。
Invasive breast cancer cells have the ability to extend membrane protrusions, invadopodia, into the extracellular matrix (EC). These structures are associated with sites of active matrix degradation. The amount of matrix degradation associated with the activity of these membrane protrusions has been shown to directly correlate with invasive potential. We demonstrate here that microinjection of polyclonal anti-cortactin antibodies blocks matrix degradation at invadopodia supporting the hypothesis that cortactin has a direct role in invasive behavior. MDA-MB-231, invasive breast cancer cells were sheared from the surface of a gelatin matrix to isolate invadopodia. Cortactin, paxillin and protein kinase C (PKC) mu, a serine kinase, were co-immunoprecipitated as a complex from invadopodia-enriched membranes. We confirmed the subcellular distribution of these proteins by immunolocalization and Western blotting. We also determined that, in contrast to its presence in invasive cells, this complex of proteins was not detected in lysates from non-invasive cells that do not form invadopodia. Taken together, these data suggest that the formation of this cortactin-containing complex correlates,vith cellular invasiveness. We hypothesize that this complex of molecules has a role in the formation and function of invadopodia during cellular invasion.