Poster Title

Exposure to Chromium (VI) Enhances the Motility of Colorectal Cancer Cells through Activation of FAK

Presenter Information

David ChenFollow

Grade Level at Time of Presentation

Sophomore

Institution

University of Kentucky

KY House District #

88

KY Senate District #

28

Department

Center for Research on Environmental Disease

Abstract

Introduction

Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. The incidence and mortality of CRC are high in the Appalachian region, including Kentucky. CRC patients in this region are mostly in advanced stages at diagnosis. In addition, high concentrations of heavy metals, such as hexavalent chromium [Cr (VI)], are found in the drinking water and soil in rural Appalachian Kentucky. Since Cr (VI) is a carcinogen, we hypothesize that chromium (VI) enhances the motility of CRC cells. Moreover, focal adhesion kinase (FAK) has been well known in regulating cell motility. Therefore, the role of FAK in Cr (VI)-enhanced motility of CRC cells was examined.

Methods

Two CRC cell lines, DLD-1 and HT29, were exposed to Cr (VI). The cell motility was determined by wound healing assay. Cellular viability was examined using MTT assay and western blot was performed to investigate the cell signaling.

Results

Exposure to Cr (VI) at 0.5 or 1 µM for 24 or 48 hours significantly increased the motility of CRC cells in a dose-dependent manner compared with the control groups. MTT results indicated that Cr (VI) treatments did not affect cellular proliferation. In addition, Cr (VI) activated FAK and its downstream signals, Src, p130cas and paxillin. Co-treatment with a specific FAK inhibitor blocked the activation of FAK-Src signaling and attenuated Cr-enhanced cell motility. Similar results were observed in both DLD-1 and HT29 cells.

Conclusion

Exposure to chromium (VI) activated FAK and enhanced the motility of CRC cells. Inhibition of FAK attenuated Cr (VI)-enhanced cell motility. Therefore, activation of FAK signaling may be a mechanism underlying colon cancer aggressiveness observed in the CRC patients of Appalachian Kentucky, a region with a high content of heavy metals.

This document is currently not available here.

Share

COinS
 

Exposure to Chromium (VI) Enhances the Motility of Colorectal Cancer Cells through Activation of FAK

Introduction

Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. The incidence and mortality of CRC are high in the Appalachian region, including Kentucky. CRC patients in this region are mostly in advanced stages at diagnosis. In addition, high concentrations of heavy metals, such as hexavalent chromium [Cr (VI)], are found in the drinking water and soil in rural Appalachian Kentucky. Since Cr (VI) is a carcinogen, we hypothesize that chromium (VI) enhances the motility of CRC cells. Moreover, focal adhesion kinase (FAK) has been well known in regulating cell motility. Therefore, the role of FAK in Cr (VI)-enhanced motility of CRC cells was examined.

Methods

Two CRC cell lines, DLD-1 and HT29, were exposed to Cr (VI). The cell motility was determined by wound healing assay. Cellular viability was examined using MTT assay and western blot was performed to investigate the cell signaling.

Results

Exposure to Cr (VI) at 0.5 or 1 µM for 24 or 48 hours significantly increased the motility of CRC cells in a dose-dependent manner compared with the control groups. MTT results indicated that Cr (VI) treatments did not affect cellular proliferation. In addition, Cr (VI) activated FAK and its downstream signals, Src, p130cas and paxillin. Co-treatment with a specific FAK inhibitor blocked the activation of FAK-Src signaling and attenuated Cr-enhanced cell motility. Similar results were observed in both DLD-1 and HT29 cells.

Conclusion

Exposure to chromium (VI) activated FAK and enhanced the motility of CRC cells. Inhibition of FAK attenuated Cr (VI)-enhanced cell motility. Therefore, activation of FAK signaling may be a mechanism underlying colon cancer aggressiveness observed in the CRC patients of Appalachian Kentucky, a region with a high content of heavy metals.