Polarised clathrin-mediated endocytosis of EGFR during chemotactic invasion.
Polarised clathrin-mediated endocytosis of EGFR during chemotactic invasion.
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DOI：
10.1111/tra.12165
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发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
Rappoport JZ
中科院分区：
文献类型：
--
作者：
Mutch LJ;Howden JD;Jenner EP;Poulter NS;Rappoport JZ
定向细胞迁移对包括发育和伤口愈合在内的许多生理过程至关重要。然而，趋化性在癌症进展过程中也被利用。最近的报道提出了囊泡运输途径和定向细胞迁移之间的联系。在转移过程中，我们对内吞作用途径的潜在作用知之甚少。因此，我们进行了一系列研究，采用先前表征的癌细胞趋化侵袭模型来评估可能将内吞作用与定向细胞迁移联系起来的特定假设。我们的研究结果表明，网格蛋白介导的内吞作用对于表皮生长因子（EGF）定向的MDA-MB-231细胞的趋化侵袭是必不可少的。相反，在这种迁移模式中不需要腔泡内吞作用。我们进一步发现，化学引诱受体（EGFR）的运输通过网格蛋白介导的内吞作用发生，并向迁移细胞的前部极化。然而，在这个迁移模型中，我们没有发现网格蛋白介导的内吞作用在局灶黏附分解中的作用。因此，本研究表征了趋化侵袭过程中内吞作用的作用，并确定了网格蛋白介导的内吞作用与定向细胞运动的机制联系。
Directed cell migration is critical for numerous physiological processes including development and wound healing. However chemotaxis is also exploited during cancer progression. Recent reports have suggested links between vesicle trafficking pathways and directed cell migration. Very little is known about the potential roles of endocytosis pathways during metastasis. Therefore we performed a series of studies employing a previously characterised model for chemotactic invasion of cancer cells to assess specific hypotheses potentially linking endocytosis to directed cell migration. Our results demonstrate that clathrin-mediated endocytosis is indispensable for epidermal growth factor (EGF) directed chemotactic invasion of MDA-MB-231 cells. Conversely, caveolar endocytosis is not required in this mode of migration. We further found that chemoattractant receptor (EGFR) trafficking occurs by clathrin-mediated endocytosis and is polarised towards the front of migrating cells. However, we found no role for clathrin-mediated endocytosis in focal adhesion disassembly in this migration model. Thus, this study has characterised the role of endocytosis during chemotactic invasion and has identified functions mechanistically linking clathrin-mediated endocytosis to directed cell motility.
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影响因子：
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