Inhibition of MCT1 to Reduce Tumor Invasion During Early Malignant Progression in HNSCC

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a widespread and common cancer, ranking as the sixth most prevalent form of cancer within the last decade. Treatment resistance and tumor persistence are large contributing factors to the mortality of HNSCC. One mechanism of treatment resistance is the maintenance of stem cell-like properties of cancer cells and their subsequent adaptability to changes in the tumor microenvironment (TME). Monocarboxylate transporter-1 (MCT1) is an important transport protein that aids in cancer cell invasion, supports cell growth, and improves cell adaptivity in the TME through transport of important monocarboxylates. This study aimed to inhibit MCT1 both genetically through CRISPR/Cas9 gene editing and pharmacologically through use of AZD3965, an MCT1 inhibitor, in order to measure the effect of cancer cell invasion and determine if MCT1 can be a therapeutic target for HNSCC. Genetic knockout of MCT1 led to substantial decreases in invasion of an HNSCC cell line; pharmacological inhibition of MCT1 also decreased invasion, though not significantly. These findings suggest that MCT1 plays a major role in the invasion of HNSCC cells and targeting this protein may provide novel solutions to treating resistant HNSCC.