YB-1 alters MT1-MMP trafficking and stimulates MCF-7 breast tumor invasion and metastasis.

YB-1 alters MT1-MMP trafficking and stimulates MCF-7 breast tumor invasion and metastasis.
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DOI:
10.1016/j.bbrc.2010.06.104
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发表时间:
2010-07-30
影响因子:
3.1
通讯作者:
Mertens, Peter R.
Mertens, Peter R.
中科院分区:
生物学4区
文献类型:
--
作者:
Lovett, David H.;Cheng, Sunfa;Cape, Leslie;Pollock, Allan S.;Mertens, Peter R.

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YB-1是冷休克结构域家族的成员,在DNA结构、基因转录和翻译中具有复杂的作用。YB-1促进染色体不稳定性,乳腺转基因表达诱导肿瘤100%转化率。YB-1与乳腺癌的不良预后有关,并且是复发和疾病特异性生存的强预测因子。生存率与局部浸润和远端转移的程度直接相关,这些过程依赖于膜I型基质金属蛋白酶MT 1-MMP的活性。用YB-1/EGFP转染非侵袭性MCF-7乳腺癌细胞。在具有迁移表型的细胞的侵袭伪足中检测到YB-1蛋白。MT 1-MMP蛋白表达增加,集中在运动细胞的前缘,在胶原三维培养中具有高度侵袭性。MT 1-MMP蛋白的内吞和再循环到细胞表面的速率在表达较高水平的YB-1蛋白的克隆中升高。对照MCF-7细胞在体内形成非致命的、非侵袭性的分化腺癌。YB-1表达增加2倍的MCF-7细胞形成高度间变性肿瘤,具有局部浸润、肺转移和高致死性。我们的结论是,YB-1有助于发展的侵袭性,转移性乳腺癌表型的增强MT 1-MMP的介绍在网站的细胞侵袭。
YB-1 is a member of the cold shock domain family, with complex roles in DNA structure, gene transcription and translation. YB-1 promotes chromosomal instability, and mammary gland transgenic expression induces tumors with 100% penetrance. YB-1 is linked to poor prognosis in breast carcinoma and is a strong predictor of relapse and disease-specific survival. Survival is directly tied to the extent of local invasion and distal metastasis, processes dependent upon the activity of the membrane type I-matrix metalloproteinase, MT1-MMP. Non-invasive MCF-7 breast adenocarcinoma cells were transfected with YB-1/EGFP. YB-1 protein was detected in the invadopodia of cells with a migratory phenotype. There was increased expression of MT1-MMP protein concentrated at the leading edges of motile cells, which were highly invasive in collagen three-dimensional culture. The rates of MT1-MMP protein endocytosis and recycling to the cell surface were elevated in clones expressing higher levels of YB-1 protein. Control MCF-7 cells formed nonfatal, noninvasive, differentiated adenocarcinomas in vivo. MCF-7 cells expressing a two-fold increase in YB-1 formed highly anaplastic tumors with local invasion, pulmonary metastases and high lethality. We conclude that YB-1 contributes to the development of an invasive, metastatic breast carcinoma phenotype by enhanced presentation of MT1-MMP at the sites of cellular invasion.
重新定义了乳腺癌的预后因素:YB-1比雌激素受体或HER-2在所有肿瘤亚型中比雌激素受体或HER-2更强的预测指标。
DOI: 10.1186/bcr2156
发表时间: 2008
期刊: Breast cancer research : BCR
影响因子: --
作者:
Habibi G;Leung S;Law JH;Gelmon K;Masoudi H;Turbin D;Pollak M;Nielsen TO;Huntsman D;Dunn SE
通讯作者: Dunn SE
DOI: 10.1038/sj.emboj.7601606
发表时间: 2007-03-21
期刊: EMBO JOURNAL
影响因子: 11.4
作者:
Bravo-Cordero, Jose J.;Marrero-Diaz, Raquel;Montoya, Maria C.
通讯作者: Montoya, Maria C.
DOI: 10.1074/jbc.272.36.22905
发表时间: 1997-09-05
影响因子: 4.8
作者:
Mertens, PR;Harendza, S;Lovett, DH
通讯作者: Lovett, DH
DOI: 10.1242/jcs.00710
发表时间: 2003-10-01
影响因子: 4
作者:
Remacle, A;Murphy, G;Roghi, C
通讯作者: Roghi, C
DOI: 10.1016/s0092-8674(03)00513-0
发表时间: 2003-07-11
期刊: CELL
影响因子: 64.5
作者:
Hotary, KB;Allen, ED;Weiss, SJ
通讯作者: Weiss, SJ