Abstract

Abstract Purpose: Snail and serpin peptidase inhibitor clade A member 1 (serpinA1) are involved in tumor progression. In this study, we investigated the role of Snail and serpinA1 in colorectal cancer (CRC) and examined the mechanisms through which these proteins mediate CRC progression. Experimental Design: Tumors from 528 patients with CRC were examined to determine the clinicopathological significance of Snail and serpinA1 expression. Cell migration and invasion were assessed to determine the functional roles of Snail and serpinA1. Snail binding to the serpinA1 promoter was analyzed by chromatin immunoprecipitation (ChIP) assays. Results: Immunohistochemical analysis of 528 samples from patients with CRC showed that elevated expression of Snail or serpinA1 was correlated with advanced stage, lymph node metastasis, and poor prognosis. Moreover, we detected a correlation between Snail and serpinA1 expression. Functional studies performed using the CRC cell lines DLD-1 and SW-480 showed that overexpression of Snail or serpinA1 significantly increased CRC cell invasion and migration. Conversely, knockdown of Snail or serpinA1 expression suppressed CRC cell invasion and migration. ChIP analysis revealed that Snail regulated serpinA1 by binding to its promoter. In addition, fibronectin mediated Snail and serpinA1 signaling and was involved in CRC cell invasion and migration. Conclusion: Taken together, our data showed that Snail and serpinA1 promoted CRC progression through fibronectin. These findings suggested that Snail and serpinA1 were novel prognostic biomarkers and candidate therapeutic targets in CRC. Note: This abstract was not presented at the meeting. Citation Format: Chae Hwa Kwon, Hye Ji Park, Ja Rang Lee, Hye Kyung Kim, Do Youn Park. Snail and serpinA1 promote tumor progression and predict prognosis in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3417. doi:10.1158/1538-7445.AM2015-3417

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