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Abstract:
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Background: Epithelial-mesenchymal transition is a critical early event in the invasion and metastasis of many cancers, including colorectal cancer. Chronic inflammation is an inducer of several cancers and inflammatory cytokines have been implicated in tumor invasion. Materials and Methods: Human colon cancer cell lines HCT116 and SW480 were transfected with PTEN siRNA or non-targeting control. Invasiveness was measured using a modified Boyden chamber assay and migration was assessed using a scratch assay. Results. PTEN knockdown increases the invasion and migration of CRC cells and the addition of medium containing TNF-á further enhanced the migration and invasion. PTEN knockdown resulted in nuclear â-catenin accumulation and increased expression of downstream proteins c-Myc and cyclin D1. Conclusions. Our study supports clinical studies identifying an association of PTEN loss with late stage cancer. Cellular factors secreted from the surrounding tumor milieu likely act in concert with genetic changes in the tumor cells and contribute to enhanced tumor invasion. |