The Runx transcriptional co-activator, CBFbeta, is essential for invasion of breast cancer cells.
The Runx transcriptional co-activator, CBFbeta, is essential for invasion of breast cancer cells.
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DOI：
10.1186/1476-4598-9-171
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发表时间：
2010-06-30
期刊：
影响因子：
37.3
通讯作者：
Shore P
中科院分区：
文献类型：
--
作者：
Mendoza-Villanueva D;Deng W;Lopez-Camacho C;Shore P
转录因子Runx 2在转移到骨的癌症中具有确定的作用。在转移性乳腺癌细胞中，Runx 2过表达，并通过调节几种侵袭基因的表达来促进细胞的侵袭能力。CBFβ是一种转录辅激活因子，由Runx转录因子募集到启动子，有大量证据表明CBFβ对Runx因子的功能至关重要。然而，Runx 1的过表达可以部分挽救CBFβ缺陷小鼠的致死表型，表明Runx因子水平的增加在某些情况下可以克服对CBFβ的需求。由于Runx 2在转移性乳腺癌细胞中过表达，并且没有关于CBFβ在乳腺细胞中表达的报道，我们试图确定Runx 2在这些细胞中的功能是否依赖于CBFβ。这种相互作用可能代表了一个可行的治疗干预，以抑制骨转移的目标。我们发现CBFβ在转移性乳腺癌细胞MDA-MB-231中表达，并且它与Runx 2相关。采用Matrigel侵袭实验和RNA干扰技术证明CBFβ参与了这些细胞的侵袭能力。随后对MDA-MB-231细胞中Runx 2靶基因的分析表明，CBFβ对于骨桥蛋白、基质金属蛋白酶-13、基质金属蛋白酶-9和骨钙蛋白的表达至关重要，但对于半乳凝素-3则不然。染色质免疫沉淀分析显示，CBFβ被募集到骨桥蛋白和半乳糖凝集素-3启动子。CBFβ在转移性乳腺癌细胞中表达，是细胞侵袭所必需的。CBFβ是已知参与细胞侵袭的几种Runx 2靶基因表达所必需的。然而，虽然CBFβ是入侵所必需的，但并非所有Runx 2靶基因都需要CBFβ。我们得出结论，CBFβ是Runx 2靶基因子集所必需的，足以维持细胞的侵袭性表型。这些发现表明，Runx 2和CBFβ之间的相互作用可能是治疗干预抑制骨转移的可行靶点。
The transcription factor Runx2 has an established role in cancers that metastasize to bone. In metastatic breast cancer cells Runx2 is overexpressed and contributes to the invasive capacity of the cells by regulating the expression of several invasion genes. CBFβ is a transcriptional co-activator that is recruited to promoters by Runx transcription factors and there is considerable evidence that CBFβ is essential for the function of Runx factors. However, overexpression of Runx1 can partially rescue the lethal phenotype in CBFβ-deficient mice, indicating that increased levels of Runx factors can, in some situations, overcome the requirement for CBFβ. Since Runx2 is overexpressed in metastatic breast cancer cells, and there are no reports of CBFβ expression in breast cells, we sought to determine whether Runx2 function in these cells was dependent on CBFβ. Such an interaction might represent a viable target for therapeutic intervention to inhibit bone metastasis. We show that CBFβ is expressed in the metastatic breast cancer cells, MDA-MB-231, and that it associates with Runx2. Matrigel invasion assays and RNA interference were used to demonstrate that CBFβ contributes to the invasive capacity of these cells. Subsequent analysis of Runx2 target genes in MDA-MB-231 cells revealed that CBFβ is essential for the expression of Osteopontin, Matrixmetalloproteinase-13, Matrixmetalloproteinase-9, and Osteocalcin but not for Galectin-3. Chromatin immunoprecipitation analysis showed that CBFβ is recruited to both the Osteopontin and the Galectin-3 promoters. CBFβ is expressed in metastatic breast cancer cells and is essential for cell invasion. CBFβ is required for expression of several Runx2-target genes known to be involved in cell invasion. However, whilst CBFβ is essential for invasion, not all Runx2-target genes require CBFβ. We conclude that CBFβ is required for a subset of Runx2-target genes that are sufficient to maintain the invasive phenotype of the cells. These findings suggest that the interaction between Runx2 and CBFβ might represent a viable target for therapeutic intervention to inhibit bone metastasis.
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影响因子：
5.3
作者：
Inman, CK;Li, N;Shore, P
通讯作者：
Shore, P
影响因子：
4
作者：
Coffman, James A.
通讯作者：
Coffman, James A.
DOI：
10.1073/pnas.0409121102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Javed, A;Barnes, GL;Stein, GS
通讯作者：
Stein, GS
DOI：
10.1073/pnas.93.8.3444
发表时间：
1996-04-16
影响因子：
11.1
作者：
Wang, Q;Stacy, T;Speck, NA
通讯作者：
Speck, NA
影响因子：
4.8
作者：
Selvamurugan, N;Kwok, S;Partridge, NC
通讯作者：
Partridge, NC