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Eps8调控鳞状癌细胞中Src和粘着斑激酶依赖性表型。

Eps8 controls Src- and FAK-dependent phenotypes in squamous carcinoma cells.

作者信息

Schoenherr Christina, Serrels Bryan, Proby Charlotte, Cunningham Debbie L, Findlay Jane E, Baillie George S, Heath John K, Frame Margaret C

机构信息

Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, EH4 2XR Edinburgh, UK.

Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.

出版信息

J Cell Sci. 2014 Dec 15;127(Pt 24):5303-16. doi: 10.1242/jcs.157560. Epub 2014 Oct 29.

DOI:10.1242/jcs.157560
PMID:25359883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4265741/
Abstract

Eps8 is an actin regulatory scaffold protein whose expression is increased in squamous cell carcinoma (SCC) cells. It forms a complex with both focal adhesion kinase (FAK, also known as PTK2) and Src in SCC cells derived from skin carcinomas induced by administration of the chemical DMBA followed by TPA (the DMBA/TPA model). Here, we describe two new roles for Eps8. Firstly, it controls the spatial distribution of active Src in a FAK-dependent manner. Specifically, Eps8 participates in, and regulates, a biochemical complex with Src and drives trafficking of Src to autophagic structures that SCC cells use to cope with high levels of active Src when FAK is absent. Secondly, when FAK is expressed in SCC cells, thereby meaning active Src becomes tethered at focal adhesion complexes, Eps8 is also recruited to focal adhesions and is required for FAK-dependent polarization and invasion. Therefore, Eps8 is a crucial mediator of Src- and FAK-regulated processes; it participates in specific biochemical complexes and promotes actin re-arrangements that determine the spatial localization of Src, and modulates the functions of Src and FAK during invasive migration.

摘要

Eps8是一种肌动蛋白调节支架蛋白，其在鳞状细胞癌（SCC）细胞中的表达增加。在通过给予化学物质DMBA后再给予TPA诱导的皮肤癌衍生的SCC细胞（DMBA/TPA模型）中，它与粘着斑激酶（FAK，也称为PTK2）和Src形成复合物。在此，我们描述了Eps8的两个新作用。首先，它以FAK依赖的方式控制活性Src的空间分布。具体而言，Eps8参与并调节与Src的生化复合物，并驱动Src向自噬结构的转运，当缺乏FAK时，SCC细胞利用这些自噬结构来应对高水平的活性Src。其次，当FAK在SCC细胞中表达时，这意味着活性Src会被束缚在粘着斑复合物上，Eps8也会被招募到粘着斑，并且是FAK依赖的极化和侵袭所必需的。因此，Eps8是Src和FAK调节过程的关键介质；它参与特定的生化复合物，促进肌动蛋白重排，从而决定Src的空间定位，并在侵袭性迁移过程中调节Src和FAK的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0171/4265741/a689b81c5a7c/jcs-127-24-5303-f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0171/4265741/4dbe943846e6/jcs-127-24-5303-f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0171/4265741/bd590bf583a6/jcs-127-24-5303-f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0171/4265741/106c03b1ab6a/jcs-127-24-5303-f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0171/4265741/5dc39d2a53fc/jcs-127-24-5303-f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0171/4265741/65d6311c0d48/jcs-127-24-5303-f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0171/4265741/a689b81c5a7c/jcs-127-24-5303-f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0171/4265741/4dbe943846e6/jcs-127-24-5303-f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0171/4265741/bd590bf583a6/jcs-127-24-5303-f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0171/4265741/106c03b1ab6a/jcs-127-24-5303-f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0171/4265741/5dc39d2a53fc/jcs-127-24-5303-f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0171/4265741/65d6311c0d48/jcs-127-24-5303-f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0171/4265741/a689b81c5a7c/jcs-127-24-5303-f06.jpg

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