Introduction In search of a valid prognostic marker for HNSCC, NOTCH1 came up as the second most
common mutated gene in whole-exome sequencing of HNSCC specimen. The aim of this project
is to get further insight into the underlying functional mechanisms of NOTCH1 in HNSCC,
potentially establishing NOTCH1 as a prognostic marker or therapeutic target for HNSCC.
Methods NOTCH1 was knocked down via RNA interference in 3 HPV-positive and 3 HPV-negative
cell lines and the impact was evaluated in various functional assays. Additionally,
cells were treated with DAPT or DLL4, an inhibitor or stimulator of NOTCH1-receptor,
respectively. Mediators of the signaling pathway were assessed by Western blot. Afterwards
the expression of NOTCH1, CD3 and CD8 was examined by immunohistochemistry in 74 oropharyngeal
squamous cell cancer FFPE tissue samples.
Conclusions Knockdown of NOTCH1 resulted in a significant decrease in migration, proliferation
and invasion, whereas the NOTCH1 ligand DLL4 could increase proliferation and invasion
of HNSCC cells. These findings were independent from HPV status. Western blotting
of the Knockdown revealed a reduction of AKT, EGFR and MEK. In our IHC cohort, NOTCH1
was upregulated in OPSCC and a high expression was associated with advanced T stage.
Conclusions NOTCH1 is involved in migration, invasion and proliferation of HNSCC cell lines.
These findings are consistent with in vivo correlation of the increased NOTCH1 expression
and advanced T stage in OPSCC. Overall, NOTCH1 seems to have a bimodal role as an
oncogene and tumor suppressor in HNSCC.
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