p63/MT1-MMP axis is required for in situ to invasive transition in basal-like breast cancer
p63/MT1-MMP axis is required for in situ to invasive transition in basal-like breast cancer
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DOI：
10.1038/onc.2015.87
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发表时间：
2016-01-21
期刊：
影响因子：
8
通讯作者：
Chavrier, P.
中科院分区：
文献类型：
--
作者：
Lodillinsky, C.;Infante, E.;Chavrier, P.
导管原位癌（DCIS）向浸润性乳腺癌的转变需要肿瘤细胞穿过基底膜（BM）。然而，BM迁移的机制知之甚少。在这里，我们报告，表达的膜型1（MT 1）-基质金属蛋白酶（MMP），一个关键组成部分的BM侵袭程序，增加乳腺癌的进展过程中，在原位浸润性乳腺癌的过渡。在导管内异种移植模型中，MT 1-MMP是MCF 10 DCIS的BM迁移所必需的。com乳腺癌细胞中，并在覆盖病灶BM破坏的细胞簇和浸润性肿瘤前沿过表达。p63和MT 1-MMP在MCF 10 DCIS边缘处表达显著上调。com异种移植肿瘤和p63是诱导响应微环境信号的MT 1-MMP依赖性侵入程序所必需的。免疫组化和公共数据库分析显示，p63和MT 1-MMP在人类基底细胞样乳腺癌中上调，提示p63/MT 1-MMP轴有助于基底细胞样乳腺癌的进展，其中p63和MT 1-MMP水平升高。
The transition of ductal carcinoma in situ (DCIS) to invasive breast carcinoma requires tumor cells to cross the basement membrane (BM). However, mechanisms underlying BM transmigration are poorly understood. Here, we report that expression of membranetype 1 (MT1)-matrix metalloproteinase (MMP), a key component of the BM invasion program, increases during breast cancer progression at the in situ to invasive breast carcinoma transition. In the intraductal xenograft model, MT1-MMP is required for BM transmigration of MCF10DCIS. com breast adenocarcinoma cells and is overexpressed in cell clusters overlying focal BM disruptions and at the invasive tumor front. Mirrored upregulation of p63 and MT1-MMP is observed at the edge of MCF10DCIS. com xenograft tumors and p63 is required for induction of MT1-MMP-dependent invasive program in response to microenvironmental signals. Immunohistochemistry and analysis of public database reveal that p63 and MT1-MMP are upregulated in human basal-like breast tumors suggesting that p63/MT1-MMP axis contributes to progression of basal-like breast cancers with elevated p63 and MT1-MMP levels.