MT1-MMP protects breast carcinoma cells against type I collagen-induced apoptosis
MT1-MMP protects breast carcinoma cells against type I collagen-induced apoptosis
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DOI：
10.1038/onc.2011.249
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发表时间：
2012-01-01
期刊：
影响因子：
8
通讯作者：
Noel, A.
中科院分区：
文献类型：
--
作者：
Maquoi, E.;Assent, D.;Noel, A.
当侵入的乳腺癌细胞突破其底层基底膜时，它们会遇到以 I 型胶原蛋白为主的致密三维反应性基质。为了发展转移能力，入侵的肿瘤细胞必须获得适应这种新微环境的能力。胶原蛋白通过诱导细胞凋亡来影响上皮细胞的命运。然而，侵入肿瘤细胞逃避胶原诱导的细胞凋亡的机制仍有待确定。我们证明，膜 1 型基质金属蛋白酶 (MT1-MMP/MMP-14) 使乳腺癌细胞在嵌入胶原凝胶中和体内原位植入后能够逃避细胞凋亡。在缺乏 MMP-14 依赖性蛋白水解作用的情况下，I 型胶原通过诱导管腔样乳腺癌细胞中促凋亡 Bcl-2 相互作用杀伤剂的表达来引发细胞凋亡。这些发现揭示了 MMP-14 活性通过规避细胞凋亡促进肿瘤进展的新机制。癌基因 (2012) 31, 480-493; doi：10.1038/onc.2011.249； 2011 年 6 月 27 日在线发布
As invading breast carcinoma cells breach their underlying basement membrane, they become confronted with a dense three-dimensional reactive stroma dominated by type I collagen. To develop metastatic capabilities, invading tumor cells must acquire the capacity to negotiate this novel microenvironment. Collagen influences the fate of epithelial cells by inducing apoptosis. However, the mechanisms used by invading tumor cells to evade collagen-induced apoptosis remain to be defined. We demonstrate that membrane type-1 matrix metalloproteinase (MT1-MMP/MMP-14) confers breast cancer cells with the ability to escape apoptosis when embedded in a collagen gel and after orthotopic implantation in vivo. In the absence of MMP-14-dependent proteolysis, type I collagen triggers apoptosis by inducing the expression of the pro-apoptotic Bcl-2-interacting killer in luminal-like breast cancer cells. These findings reveal a new mechanism whereby MMP-14 activity promotes tumor progression by circumventing apoptosis. Oncogene (2012) 31, 480-493; doi: 10.1038/onc.2011.249; published online 27 June 2011