Securin (hPTTG1) expression is regulated by β-catenin/TCF in human colorectal carcinoma

Abstract

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. © 2006 Cancer Research UK.