Securin (hPTTG1) expression is regulated by beta-catenin/TCF in human colorectal carcinoma.
Securin (hPTTG1) expression is regulated by beta-catenin/TCF in human colorectal carcinoma.
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Securin（HPTTG1）表达受人结肠直肠癌的β-catenin/tcf调节。
DOI：
10.1038/sj.bjc.6603155
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发表时间：
2006-06-05
影响因子：
8.8
通讯作者：
Brabletz, T
中科院分区：
文献类型：
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作者：
Hlubek, F;Pfeiffer, S;Budczies, J;Spaderna, S;Jung, A;Kirchner, T;Brabletz, T
转录激活因子β-catenin的过度表达，主要是由于腺瘤性结肠息肉病（APC）肿瘤抑制基因的功能缺失突变，是人类结直肠癌发生的起始和进展的关键。Securin是染色体分离的调节剂，其过表达已被证明参与不同的肿瘤促进过程，如转化，过度增殖和血管生成，并与肿瘤细胞侵袭相关。然而，导致结直肠癌中securin过度表达的分子机制尚不清楚。在此，我们发现β-catenin和securin（hPTTG 1）在结直肠腺瘤和癌中的相关高表达，并进一步证明securin是β-catenin转录激活的靶点。这意味着β-连环蛋白/T细胞因子信号通路的失调导致人结直肠癌中securin的过度表达，这随后可能有助于肿瘤进展。
Overexpression of the transcriptional activator β-catenin, mostly owing to loss-of-function mutations of the adenomatous polyposis coli (APC) tumour suppressor gene, is crucial for the initiation and progression of human colorectal carcinogenesis. Securin is a regulator of chromosome separation and its overexpression has been shown to be involved in different tumour-promoting processes, like transformation, hyperproliferation and angiogenesis, and correlates with tumour cell invasion. However, the molecular mechanism leading to securin overexpression in human colorectal cancer is unknown. Here we show a correlated high expression of β-catenin and securin (hPTTG1) in colorectal adenomas and carcinomas and further demonstrate that securin is a target of β-catenin transcriptional activation. This implies that deregulation of the β-catenin/T-cell factor-signalling pathway leads to overexpression of securin in human colorectal cancer, which subsequently may contribute to tumour progression.