Background

MMP-1 (Matrix metalloproteinase-1) promotes carcinogenesis and distant metastasis in different cancers. Regulation of MMP-1 could occur at multiple levels: epigenetically, post-transcriptionally, or post-translationally. An increasing body of evidence supports that the cytoplasmic transcription factor STAT3 (signal transducer and activator of transcription 3) is activated constitutively in a variety of cancers wherein it significantly affects the growth of tumors and also facilitates metastasis. In addition, STAT3 has been found to regulate nuclear activity pro-inflammatory transcriptional factor, NF-κB signaling, especially, the alternative one (RelB/p100) by directly interacting with them

Method and Results

In this proof of concept study, we tested the hypothesis that STAT3 interacts with RelB to promote tumor invasion by positively regulating MMP-1 in colon cancer. We found that RelB and STAT3 were constitutively localized in the nucleus of colon cancer in surgically-resected specimens with use of Western blot analysis, which was further confirmed by immunofluorescence (IF) staining in colon carcinoma cell line HT29. We further observed that STAT3/RelB knockdown resulted in reduced MMP-1. Our results from chromatin immunoprecipitation studies further established that association between RelB and MMP-1 promoter decreased when STAT3 was depleted, and conversely, STAT3 association with MMP-1 decreased with the knockdown of RelB.

Conclusion

These results suggest that STAT3 and ReB constitute a minimal activator complex for positive regulation of MMP-1 in colon cancer

中文翻译：

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STAT3和RelB的相互作用调节MMP-1在结肠癌中的作用

背景

MMP-1（基质金属蛋白酶-1）促进不同癌症中的癌变和远处转移。MMP-1的调节可能发生在多个水平：表观遗传，转录后或翻译后。越来越多的证据支持细胞质转录因子STAT3（信号转导子和转录激活子3）在多种癌症中被组成性激活，其中它显着影响肿瘤的生长并促进转移。此外，已发现STAT3通过与核转录因子直接相互作用来调节核活性促炎转录因子NF-κB信号，特别是另一种转录因子（RelB / p100）。

方法与结果

在此概念验证研究中，我们测试了STAT3与RelB相互作用以通过积极调节结肠癌中MMP-1促进肿瘤侵袭的假设。我们发现RelB和STAT3组成性地定位在手术切除的标本中的结肠癌细胞核中，使用Western印迹分析，这在结肠癌细胞系HT29中通过免疫荧光（IF）染色进一步证实。我们进一步观察到，STAT3 / RelB敲低导致MMP-1减少。我们从染色质免疫沉淀研究得到的结果进一步证明，当STAT3耗尽时，RelB和MMP-1启动子之间的结合会减少，反之，随着RelB的敲低，STAT3与MMP-1的结合会减少。

结论

这些结果表明，STAT3和ReB构成了结肠癌中MMP-1阳性调节的最小激活物复合物。