Differential activation of NOTCH1 pathway in HNSCC cell lines of different anatomical sites

Abstract

Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent types of cancers and the role of NOTCH1 pathway during development of HNSCC is debatable. Here, we have made an attempt to evaluate the NOTCH1 pathway status in HNSCC cell lines from different anatomical subsites. At first, mRNA expression status of NOTCH1 pathway associated genes (NOTCH1/JAG1/JAG2/HES1/HEY1/CD44/FBXW7/HIF1α/VEGF) was analysed in two HNSCC cell lines: FaDu (hypopharyngeal carcinoma) and SCC9 (tongue carcinoma) and was compared with publicly available database. Then, molecular profiling (RNA/protein) of the genes and cell cycle phase distribution analysis were done after DAPT (γ-secretase inhibitor) administration at different concentrations on the cell lines to see the differential effect, if any. High NOTCH1 pathway activation was noted in FaDu cell line than the SCC9. In cytotoxicity assay with DAPT, FaDu showed more sensitivity than SCC9. Therefore, gradual decline of the expression of NOTCH1 pathway associated genes was noted in FaDu with the increasing DAPT concentrations, leading to high S/G2-M arrest of the cell population. Contrastingly, SCC9 showed significant reduced expression of the genes at higher concentration of DAPT with comparatively low S/G2-M arrest of the cell population. The study demonstrates distinct NOTCH1 pathway signature in the HNSCC cell lines of specific sub-sites of head and neck.