Mucin 1 regulates the hypoxia response in head and neck cancer cells

Abstract

Mucin 1 (MUC1) is a transmembrane glycoprotein that contributes to the cellular response in hypoxic conditions in different carcinomas. We investigated the gene expression pattern of MUCs (1, 2, 4, 5AC, 5B, 6, 15, 16, and 19) in isogenic primary (HN4 and HN30) and metastatic (HN12 and HN31) head and neck squamous cell carcinoma (HNSCC) cell lines. MUC1 was significantly up-regulated at the mRNA and protein levels in HN12 and HN31 cells, whereas, other MUCs exhibited diverse expression patterns between HNSCC cell lines. Immunohistochemistry demonstrated that MUC1 was exclusively expressed in cancer cells; however, there was no significant correlation between MUC1 expression and malignancy grading. Inducing hypoxia with CoCl₂ significantly increased cell viability, MUC1, hypoxia-inducible factor alpha (HIF-1α), and vascular endothelial growth factor A (VEGF-A) expression in HN12 cells, but not HN31 cells. Interestingly, in hypoxia, cell viability, HIF-1α and VEGF-A expression were significantly reduced in MUC1-knockdown HN12 cells. The current report is the first to demonstrate that MUC1 is required in the regulation of hypoxia-related genes in HNSCC cells. Thus, our results suggest that MUC1 modulates the hypoxic effects in HNSCC cells through HIF-1α regulation.

Keywords: Cell signaling; Head and neck squamous cell carcinoma; Hypoxia; Mucin 1.