Discipline: Biological Sciences
Subcategory: Cancer Research
Dameia Brewster - Alabama State University
Cancer is one of the leading cause of deaths worldwide. One of the major interests of cancer biologists is to understand the cellular processes that are disrupted during cancer progression. Cholesterol plays an important role as a modifier of signaling molecules, a precursor of steroid hormones, and component of cell membranes. However, the role of cholesterol in cancer development is still a controversial topic in the cancer community. While some studies report a link between cancer and low levels of cholesterol, others suggest that cholesterol deprivation promotes tumor cell death. Because of its important roles in the cell, we hypothesize that changes in cholesterol homeostasis will potentially affect multiple aspects of cancer biology, including cell proliferation and cell migration. In the present study, we utilized the UALCAN portal to perform an in silico screening of multiple human cancers for the expression of genes involved in cholesterol synthesis or trafficking. We found that multiple cholesterol-synthesizing genes including DHCR7 and HMGCR are misregulated in multiple cancers including breast cancer and colon cancer. Similarly, multiple cholesterol trafficking genes are dysregulated in multiple cancers. Interestingly, the misregulation of cholesterol synthesizing or trafficking genes was cancer type specific. Our current aim is to use small molecule inhibitors to compare the respective effects of the inhibition of cholesterol synthesis with HMGCR and DHCR7 inhibitors and the inhibition of cholesterol trafficking with SREBP1 and ABCA1 inhibitors on cancer cell biology. To do so, we will culture breast and colon cancer cells in the presence of each inhibitor and use cytological methods as well as molecular methods to assess changes in cell viability, migration, proliferation, and invasion compared to untreated control cells. In conclusion, we found that genes are important for cholesterol synthesis and cholesterol trafficking and differently regulate between normal tissues and human cancers. The disruption of cholesterol homeostasis might be a contributing factor to cancer progression. Our current studies are aimed to understanding the cellular and molecular consequences of disruption on cancer cells.
Funder Acknowledgement(s): MSEIP (Minority Science and Engineering Program)
Faculty Advisor: Emmanuel Tadjuidje, firstname.lastname@example.org
Role: My part of this research involved cell culturing breast cancer cells and colon cancer cells and experimenting with the presence of the different inhibitor to compare and contrast the differences in the effects of each cancer cell. Also, I worked with the UALCAN portal to perform in silico screenings of multiple human cancers for the expression of genes involved in cholesterol synthesis or trafficking.