McNair/Gateway Scholars Program USC

Demetri Euter

DemetriEuter.jpg

Major and Classification

Biological Sciences

Faculty Mentor

    Suraiya Rasheed, Ph.D.

Department

    Keck School of Medicine, Pathology

McNair Project

Proteomics and Bioinformatics Analysis of Acetylcholinesterase Expressed in Melanoma Stem Cells

Abstract
Stem-cell derived melanomas (cancer stem cells) were made known through the studies of Dr. Suraiya Rasheed's laboratory on a highly malignant cat melanoma (cell line CT1413) that differentiated into neuronal cells. In order to gain a better understanding of tumorigenesis and cell growth in melanoma tumors, Dr. Rasheed's laboratory identified 84 differentially expressed proteins in the melanoma and neuronal cells. Based on the multiple functionalities of proteins, we hypothesized that an enzyme acetylcholinesterase (AChE) which is differentially regulated between the melanoma and neuronal cells is significantly associated with the aggressive growth (stemness) of this cat melanoma cell line. To test the hypothesis, differentiated proteomics and bioinformatics analysis (2D-gel electrophoresis, image analyses and mass spectrometry) was used to identify specific proteins associated or expressed in this melanoma. AChE, which was found to be expressed in the trans-differentiated neuronal cells, was identified as an upregulated protein in the cat melanoma stem cells. Proteomics and bioinformatics analyses of the cat melanoma cells indicated that AChE is a multifunctional enzyme which is normally associated with enhanced malignant potential of the melanoma and brain tumors. AChE functions as an autocrine/paracrine growth factor in small cell lung carcinoma. During the embryonic growth, expression of AChE is essential for the development of embryonic nervous system, synaptogenic activities and growth of neurites. AChE also acts as an adhesion molecule for neural networks of connectivity and synapse. We conclude that the expression of AChE in the cat melanoma is critical for maintaining the stem-cell properties of self-renewal while retaining the cell's potential to differentiate into neuronal cells. This is shown through the functions of AChE that are specific to melanoma (promotes tumor aggressiveness, exhibits blood formation activities and regulation of inflammation). A greater understanding of how AChE as well as how other proteins interact within a stem cell environment can unlock a wealth of knowledge that can be used to develop more successful treatments for cancer.