Date of Award

2024

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Walstrom, Katherine

Area of Concentration

Biology with Chemistry

Abstract

Oral squamous cell carcinoma (OSCC) arises from the mucosal surface and is the most common type of head and neck cancer. Despite treatment, it often recurs, leading to high patient mortality. Most OSCC advances from precancerous dysplasia to early invasive cancer, but the process is not fully understood, hindering effective interventions. Monocarboxylate transporter 1 (MCT1) is a membrane protein that transports L-lactate and pyruvate across the plasma membrane. Because increased MCT1 expression is linked to OSCC progression, we hypothesized that MCT1 promotes progression by supporting metabolic coupling between cancer cells and the surrounding stroma. To test this hypothesis, we knocked out (KO) MCT1 using CRISPR/Cas9 in DOK (dysplastic) and TR146 (OSCC) cell lines. Knock-out of MCT1 was confirmed by qRT-PCR. Metabolic tests showed that DOK cells with MCT1 had higher mitochondrial activity compared to others that had moderate to low mitochondrial activity. In contrast, TR146 cells without MCT1 had higher glycolytic activity compared to other cell lines. Intriguingly, DOK cells shifted more quickly to glycolysis after mitochondrial inhibition compared to TR146 cells. But both DOK cell lines with and without MCT 1 expression switched to glycolysis. These data partially suggest MCT1 regulates the metabolism of oral dysplasia and OSCC, and changes in the metabolism of dysplasia are required for progression to OSCC.

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