ORCID

0009-0009-1767-3782

Keywords

Cancer, Colorectal Cancer, FGF19, EMT, BLU-554, FGFR4

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. With 154,000 new cases estimated in 2025, there is an increased need for early screening to detect CRC prior to metastasis. Our laboratory has focused on enteroendocrine hormone Fibroblast Growth Factor-19 (FGF19) as it is overexpressed in a subset of CRC tumors. FGF19 is an intestinal-derived hormone involved with lipid homeostasis when bound to its receptor, Fibroblast Growth Factor Receptor-4 (FGFR4). Our objective focuses on FGF19 contribution towards an epithelial-to-mesenchymal transition (EMT) and overall metastatic properties including rapid proliferation and/or increased cell motility. Immunofluorescence was used to detect FGF19 and FGFR4 in patient derived xenograft samples. Adhesion protein E-cadherin was used as an epithelial marker and intermediate filament protein Vimentin was used to indicate a mesenchymal phenotype. Tissue microarrays were used to investigate shifts in FGF19 and EMT protein expression via multiplex staining on the MACSima instrument. Late-stage CRC displayed increased localized FGF19 expression in the tumor microenvironment, and increased ratios of vimentin to E-cadherin in the tumor tissue corresponding with increasing CRC stage and grade. We then compared HCT116 CRC cells with low FGF19 to HCT116 FGF19 overexpressed cells, both in absence and presence of an FGFR4 inhibitor to assess expression of FGF19, FGFR4 and EMT markers at 6- and 24-hour timepoints. Overexpression of transduced FGF19 was clear but significant changes in EMT markers were not definitive at these early time points. However, cell analysis of a wound-healing assay showed significantly increased motility in CRC with overexpressed FGF19 compared to low FGF19. Findings support FGF19 overexpression in CRC is associated with tumor progression and metastatic characteristics, evidenced by a tendency for high FGF19 expression in undifferentiated tumors, shifting away from high E-cadherin expression in tumor cells, and/or increase in vitro tumor cell motility over time.

Completion Date

2025

Semester

Summer

Committee Chair

Altomare, Deborah

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Format

PDF

Release Date

2-15-2026

Document Type

Thesis

Campus Location

College of Medicine

Subjects

Gastrointestinal system--Cancer--Molecular aspects; Colon (Anatomy)--Cancer--Molecular aspects; Cancer cells--Motility; Metastasis--Animal models; Fibroblast growth factors

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