AdvisorSnider, Ashley J.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
EmbargoRelease after 03/22/2023
AbstractHuman colorectal cancer is the progressive accumulation of mutations that occur in the epithelial lining of the digestive tract. One-third of patients diagnosed with colorectal cancers are hereditary or familiar cancers, while the other two-thirds of patients are diagnosed with sporadic colorectal cancer. Human colon epithelial cell lines were generated from human colon epithelium and immortalized with overexpression of CDK4 and hTERT (HCEC 1CT). Subsequent cell lines were developed to model the mutations that occur in sporadic colon cancer; CTA cells have deletion of APC, an essential protein in the WNT pathway, representative of early adenoma; RPA cells mimic late-stage adenoma and are deficient in APC and P53 and overexpress mutant KRas; A1309 cells were developed via the addition of truncated APC in the RPA cell line. All four HCEC cell lines were analyzed for metabolomic and lipidomic alterations. PCA and PLS-DA analyses of untargeted lipidomics demonstrated all lines cluster independently from one another. Heatmap analysis of the top 100 most significant lipids (p-value <0.05) showed RPA and A1309 cell lines to have the most distinct lipid profiles. Therefore, RPA and A1309 were analyzed further. Volcano plots and deconstructed volcano plots demonstrated significant alterations in specific lipid classes. Pathway analysis of the altered lipids established glycerophospholipids and sphingolipids as the lipid classes with the most significant alterations. Quantitative analyses of sphingolipids revealed significant differences in ceramides and hexosylceramides between RPA and A1309 cells. These data suggest that truncation of APC alter sphingolipid metabolism. Future studies will examine the roles of ceramides and hexosylceramides in cancer cell biologies including migration, proliferation, viability, and cell cycle.
Degree ProgramGraduate College