Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia.
Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia.
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DOI：
10.1083/jcb.201306162
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发表时间：
2013-12-23
期刊：
影响因子：
--
通讯作者：
Chavrier P
中科院分区：
文献类型：
--
作者：
Monteiro P;Rossé C;Castro-Castro A;Irondelle M;Lagoutte E;Paul-Gilloteaux P;Desnos C;Formstecher E;Darchen F;Perrais D;Gautreau A;Hertzog M;Chavrier P
WASH和外囊通过使晚期内体的MT 1-MMP能够局部胞吐而促进细胞周基质降解和肿瘤细胞侵袭。在转移性扩散期间，癌细胞对细胞外基质的重塑需要形成基于肌动蛋白的质膜突起，称为侵袭伪足，其中跨膜1型基质金属蛋白酶（MT 1-MMP）积累。在这里，我们描述了外囊复合物和内体Arp 2/3激活剂Wiskott-Aldrich综合征蛋白和瘢痕同源物（WASH）之间的相互作用MT 1-MMP-含有晚期内体在浸润性乳腺癌细胞。我们发现，WASH和exocyst所需的基质降解的exocytic机制，涉及MT 1-MMP阳性晚期内体和质膜与基质接触之间的管状连接。这确保了MT 1-MMP的局灶性递送，并支持细胞周围基质降解和肿瘤细胞侵入不同病理相关的基质环境。我们的数据提示了肿瘤细胞破坏基底膜并通过肿瘤周围富含胶原蛋白的纤维组织侵入性迁移的一般机制。
WASH and exocyst promote pericellular matrix degradation and tumor cell invasion by enabling localized exocytosis of MT1-MMP from late endosomes. Remodeling of the extracellular matrix by carcinoma cells during metastatic dissemination requires formation of actin-based protrusions of the plasma membrane called invadopodia, where the trans-membrane type 1 matrix metalloproteinase (MT1-MMP) accumulates. Here, we describe an interaction between the exocyst complex and the endosomal Arp2/3 activator Wiskott-Aldrich syndrome protein and Scar homolog (WASH) on MT1-MMP–containing late endosomes in invasive breast carcinoma cells. We found that WASH and exocyst are required for matrix degradation by an exocytic mechanism that involves tubular connections between MT1-MMP–positive late endosomes and the plasma membrane in contact with the matrix. This ensures focal delivery of MT1-MMP and supports pericellular matrix degradation and tumor cell invasion into different pathologically relevant matrix environments. Our data suggest a general mechanism used by tumor cells to breach the basement membrane and for invasive migration through fibrous collagen-enriched tissues surrounding the tumor.
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DOI：
10.1038/nrm3141
发表时间：
2011-06-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
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WASH 驱动的肌动蛋白聚合导致 V-ATP 酶修复和胞吐前囊泡中和。
DOI：
10.1083/jcb.201009119
发表时间：
2011-05-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Carnell M;Zech T;Calaminus SD;Ura S;Hagedorn M;Johnston SA;May RC;Soldati T;Machesky LM;Insall RH
通讯作者：
Insall RH
影响因子：
3.7
作者：
Derivery, Emmanuel;Helfer, Emmanuele;Gautreau, Alexis
通讯作者：
Gautreau, Alexis
影响因子：
64.5
作者：
Harrington AW;St Hillaire C;Zweifel LS;Glebova NO;Philippidou P;Halegoua S;Ginty DD
通讯作者：
Ginty DD
DOI：
10.1111/j.1600-0854.2012.01353.x
发表时间：
2012-07
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Heider MR;Munson M
通讯作者：
Munson M