Mechanisms of Colorectal Cancer Progression, Proliferation, and Metastasis (2006)

Undergraduate: Veena Rao

Faculty Advisor: Brent Weston
Department: Biology

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Colorectal cancer (CRC) represents a serious health problem because CRC

tumor cells do not respond well to traditional chemotherapy. Because of

these difficulties, new CRC treatment approaches affecting CRC-related genes

are desired. It has been found that cell-surface sugars aid in the

progression of CRC. CRC cells typically carry the sugars sialyl Lewis x

(sLex) and sialyl Lewis a (sLea) on their surfaces. SLex and sLea are

produced by the fucosyltransferase (FUT) enzymes FUT3 and FUT6, which are

encoded by the FUT genes. The purpose of my research has been to determine a

method to reduce FUT enzyme activity to elucidate the role of FUT3 and FUT6 in

CRC progression. I tested a variety of drugs hypothesized to reduce FUT

activity and found that the non-steroidal anti-inflammatory drug (NSAID)

indomethacin is capable of significantly reducing FUT3 and FUT6 activity in

CRC cells. Indomethacin treatment also reduces cell proliferation in vitro.

Additionally, tumor growth rate in nude mice is significantly reduced by

indomethacin treatment. My preliminary data show that FUT gene regulation in

response to NSAIDs does not occur primarily at the transcriptional level. In

the future, I aim to further investigate FUT gene regulation through Western

blot analysis. I also plan to combine indomethacin treatment with anti-sense

oligonucleotide treatments, which have been previously found to decrease FUT

activity. This research and data collected in the future will hopefully lead

to a greater understanding of CRC and new treatments.